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Synergistic therapeutic effect of parecoxib and ilomastat combination in osteoarthritis via inhibition of IL-17/PI3K/AKT/NF-κB activity
IF 3.2 3区 医学 Q2 BIOCHEMISTRY & MOLECULAR BIOLOGY Pub Date : 2025-02-10 DOI: 10.1016/j.molimm.2025.02.005
Xiaofei Feng , Yao Ma , Yuhao Zhao , Zhenrui Zhao , Zhengdong Song , Li Lin , Wenji Wang

Background

Osteoarthritis is a degenerative disease, and current drug treatment is to give nonsteroidal anti-inflammatory drugs to relieve symptoms. The anti-inflammatory ability of parecoxib and ilomastat has been confirmed, but the synergistic effect of combined administration in osteoarthritis has not been clear.

Methods

Mouse primary chondrocytes stimulated with IL-1β were cultured. The expression levels of inflammatory cytokines and matrix metalloproteinases were investigated by western blotting, quantitative real-time polymerase chain reaction and ELISA. The effects of parecoxib and ilomastat on chondrocyte apoptosis were evaluated by flow cytometry. In addition, the rat model of osteoarthritis was established by meniscal instability, and the morphological changes of cartilage and the expression levels of related molecules were monitored using Safranin O-Fast green and immunohistochemical staining after intra-articular injection of parecoxib, ilomastat, and the combination of the two.

Results

In vitro experiments showed that the combined administration of parecoxib and ilomastat more effectively inhibited the expression of proinflammatory factors and matrix metalloproteinases compared with single drug administration. The combined drug treatment could more effectively inhibit IL-1β-induced chondrocyte apoptosis. The combined drug treatment alleviated the progression of osteoarthritis by inhibiting the IL-17/PI3K/AKT/NF-κB pathway. In addition, in vivo experiments showed that the combined administration could improve the further deterioration of the osteoarthritis rat model.

Conclusions

The combined administration of parecoxib and ilomastat to inhibit IL-17/PI3K/AKT/NF-κB transduction is beneficial to reduce the infiltration of inflammatory factors and matrix metalloproteinases in osteoarthritis.
{"title":"Synergistic therapeutic effect of parecoxib and ilomastat combination in osteoarthritis via inhibition of IL-17/PI3K/AKT/NF-κB activity","authors":"Xiaofei Feng ,&nbsp;Yao Ma ,&nbsp;Yuhao Zhao ,&nbsp;Zhenrui Zhao ,&nbsp;Zhengdong Song ,&nbsp;Li Lin ,&nbsp;Wenji Wang","doi":"10.1016/j.molimm.2025.02.005","DOIUrl":"10.1016/j.molimm.2025.02.005","url":null,"abstract":"<div><h3>Background</h3><div>Osteoarthritis is a degenerative disease, and current drug treatment is to give nonsteroidal anti-inflammatory drugs to relieve symptoms. The anti-inflammatory ability of parecoxib and ilomastat has been confirmed, but the synergistic effect of combined administration in osteoarthritis has not been clear.</div></div><div><h3>Methods</h3><div>Mouse primary chondrocytes stimulated with IL-1β were cultured. The expression levels of inflammatory cytokines and matrix metalloproteinases were investigated by western blotting, quantitative real-time polymerase chain reaction and ELISA. The effects of parecoxib and ilomastat on chondrocyte apoptosis were evaluated by flow cytometry. In addition, the rat model of osteoarthritis was established by meniscal instability, and the morphological changes of cartilage and the expression levels of related molecules were monitored using Safranin O-Fast green and immunohistochemical staining after intra-articular injection of parecoxib, ilomastat, and the combination of the two.</div></div><div><h3>Results</h3><div>In vitro experiments showed that the combined administration of parecoxib and ilomastat more effectively inhibited the expression of proinflammatory factors and matrix metalloproteinases compared with single drug administration. The combined drug treatment could more effectively inhibit IL-1β-induced chondrocyte apoptosis. The combined drug treatment alleviated the progression of osteoarthritis by inhibiting the IL-17/PI3K/AKT/NF-κB pathway. In addition, in vivo experiments showed that the combined administration could improve the further deterioration of the osteoarthritis rat model.</div></div><div><h3>Conclusions</h3><div>The combined administration of parecoxib and ilomastat to inhibit IL-17/PI3K/AKT/NF-κB transduction is beneficial to reduce the infiltration of inflammatory factors and matrix metalloproteinases in osteoarthritis.</div></div>","PeriodicalId":18938,"journal":{"name":"Molecular immunology","volume":"179 ","pages":"Pages 94-105"},"PeriodicalIF":3.2,"publicationDate":"2025-02-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143376453","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
CD96 enhances the anti-viral activity of natural killer cells by promoting Ly49H-mediated activation during mouse cytomegalovirus infection
IF 3.2 3区 医学 Q2 BIOCHEMISTRY & MOLECULAR BIOLOGY Pub Date : 2025-02-08 DOI: 10.1016/j.molimm.2025.02.001
Soichi Matsuo , Tsukasa Nabekura , Kazuko Shibuya , Akira Shibuya
Natural killer (NK) cells are cytotoxic innate lymphocytes that play a critical role in controlling viral infections. Although CD96 has been reported as an immune checkpoint molecule in tumor immunity, the role of CD96 in NK cell activity in viral infections remains undetermined. Here, we demonstrate that CD96 functions as an activating receptor on NK cells in mouse cytomegalovirus (MCMV) infection. CD96-deficient (Cd96-/-) mice exhibited a high MCMV burden, as compared with wild-type (WT) mice. CD96 augmented the effector function of NK cells expressing Ly49H, an activating NK receptor specific for the MCMV m157 protein, against m157-expressing target cells in vitro. Mechanistically, CD96 maintained the Ly49H-mediated phosphorylation of the protein tyrosine kinases Zap70 and or Syk. These findings suggest that CD96 enhances the anti-viral activity of Ly49H+ NK cells against MCMV infection.
{"title":"CD96 enhances the anti-viral activity of natural killer cells by promoting Ly49H-mediated activation during mouse cytomegalovirus infection","authors":"Soichi Matsuo ,&nbsp;Tsukasa Nabekura ,&nbsp;Kazuko Shibuya ,&nbsp;Akira Shibuya","doi":"10.1016/j.molimm.2025.02.001","DOIUrl":"10.1016/j.molimm.2025.02.001","url":null,"abstract":"<div><div>Natural killer (NK) cells are cytotoxic innate lymphocytes that play a critical role in controlling viral infections. Although CD96 has been reported as an immune checkpoint molecule in tumor immunity, the role of CD96 in NK cell activity in viral infections remains undetermined. Here, we demonstrate that CD96 functions as an activating receptor on NK cells in mouse cytomegalovirus (MCMV) infection. CD96-deficient (<em>Cd96</em><sup>-/-</sup>) mice exhibited a high MCMV burden, as compared with wild-type (WT) mice. CD96 augmented the effector function of NK cells expressing Ly49H, an activating NK receptor specific for the MCMV m157 protein, against m157-expressing target cells <em>in vitro</em>. Mechanistically, CD96 maintained the Ly49H-mediated phosphorylation of the protein tyrosine kinases Zap70 and or Syk. These findings suggest that CD96 enhances the anti-viral activity of Ly49H<sup>+</sup> NK cells against MCMV infection.</div></div>","PeriodicalId":18938,"journal":{"name":"Molecular immunology","volume":"179 ","pages":"Pages 65-70"},"PeriodicalIF":3.2,"publicationDate":"2025-02-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143349294","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Human placental mesenchymal stem cells regulate the antioxidant capacity of CD8+PD-1+ T cells through the CD73/ADO/Nrf2 pathway to protect against liver damage in mice with acute graft-versus-host disease
IF 3.2 3区 医学 Q2 BIOCHEMISTRY & MOLECULAR BIOLOGY Pub Date : 2025-02-08 DOI: 10.1016/j.molimm.2025.01.016
Wei Yan , Hengchao Zhang , Jiashen Zhang , Yaxuan Zhao , Yunhua Wu , Xiaolin Ma , Xiying Luan
Graft-versus-host disease (GVHD) constitutes a severe complication that occurs after allogeneic hematopoietic stem cell transplantation (allo-HSCT), significantly reducing the survival rate of patients. Mesenchymal stem cells (MSCs) are capable of ameliorating the tissue damage caused by GVHD through exerting immunosuppressive effects; however, the relevant mechanisms require further investigation. This study used a GVHD mouse model to explore the therapeutic effects and mechanisms of human placental mesenchymal stem cells (hPMSCs) in mitigating GVHD-induced liver injury. The findings indicated that hPMSCs reduced the proportion of CD8+PD-1+ T cells in both the liver and spleen of GVHD mice, decreased reactive oxygen species (ROS) levels, and upregulated glutathione S transferase (GST) and glutathione (GSH) levels. Consistently, this led to a decrease in the expression of liver fibrosis markers, including alpha-smooth muscle actin (α-SMA) and fibronectin (FN). Moreover, CD8+PD-1+ T cells and ROS were positively correlated with α-SMA and FN, respectively, whereas GST and GSH were negatively correlated with them. hPMSCs with low expression in CD73 attenuated this effect. In vitro studies demonstrated that hPMSCs upregulated the expression of nuclear factor-E2-related factor 2 (Nrf2) via the CD73/adenosine (ADO) pathway, regulated oxidative metabolism, and reduced the number of CD8+PD-1+ T cells. The results suggested that hPMSCs contributed to the regulation of redox homeostasis and reduced the proportion of CD8+PD-1+ T cells through the CD73/ADO/Nrf2 signaling pathway, thereby alleviating liver injury associated with GVHD.
{"title":"Human placental mesenchymal stem cells regulate the antioxidant capacity of CD8+PD-1+ T cells through the CD73/ADO/Nrf2 pathway to protect against liver damage in mice with acute graft-versus-host disease","authors":"Wei Yan ,&nbsp;Hengchao Zhang ,&nbsp;Jiashen Zhang ,&nbsp;Yaxuan Zhao ,&nbsp;Yunhua Wu ,&nbsp;Xiaolin Ma ,&nbsp;Xiying Luan","doi":"10.1016/j.molimm.2025.01.016","DOIUrl":"10.1016/j.molimm.2025.01.016","url":null,"abstract":"<div><div>Graft-versus-host disease (GVHD) constitutes a severe complication that occurs after allogeneic hematopoietic stem cell transplantation (allo-HSCT), significantly reducing the survival rate of patients. Mesenchymal stem cells (MSCs) are capable of ameliorating the tissue damage caused by GVHD through exerting immunosuppressive effects; however, the relevant mechanisms require further investigation. This study used a GVHD mouse model to explore the therapeutic effects and mechanisms of human placental mesenchymal stem cells (hPMSCs) in mitigating GVHD-induced liver injury. The findings indicated that hPMSCs reduced the proportion of CD8<sup>+</sup>PD-1<sup>+</sup> T cells in both the liver and spleen of GVHD mice, decreased reactive oxygen species (ROS) levels, and upregulated glutathione S transferase (GST) and glutathione (GSH) levels. Consistently, this led to a decrease in the expression of liver fibrosis markers, including alpha-smooth muscle actin (α-SMA) and fibronectin (FN). Moreover, CD8<sup>+</sup>PD-1<sup>+</sup> T cells and ROS were positively correlated with α-SMA and FN, respectively, whereas GST and GSH were negatively correlated with them. hPMSCs with low expression in CD73 attenuated this effect. <em>In vitro</em> studies demonstrated that hPMSCs upregulated the expression of nuclear factor-E2-related factor 2 (Nrf2) via the CD73/adenosine (ADO) pathway, regulated oxidative metabolism, and reduced the number of CD8<sup>+</sup>PD-1<sup>+</sup> T cells. The results suggested that hPMSCs contributed to the regulation of redox homeostasis and reduced the proportion of CD8<sup>+</sup>PD-1<sup>+</sup> T cells through the CD73/ADO/Nrf2 signaling pathway, thereby alleviating liver injury associated with GVHD.</div></div>","PeriodicalId":18938,"journal":{"name":"Molecular immunology","volume":"179 ","pages":"Pages 71-83"},"PeriodicalIF":3.2,"publicationDate":"2025-02-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143350883","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Alleviation of sepsis-induced lung and liver injury by polysaccharides from Tetrastigma hemsleyanum Diels et Gilg via suppression of TLR4/NF-κB/COX-2 pathway and modulation of immune checkpoint molecules
IF 3.2 3区 医学 Q2 BIOCHEMISTRY & MOLECULAR BIOLOGY Pub Date : 2025-02-07 DOI: 10.1016/j.molimm.2025.02.002
Mengjia Zhao , Senmiao Chen , Jingwen Xu , Fangmei Zhou , Mingyuan Zhou , Shasha Tian , Zhishan Ding , Yuchi Chen
Sepsis, a common clinical complication, leads to multi-organ damage due to systemic infection and currently lacks effective therapeutic drugs. Polysaccharide derived from Tetrastigma hemsleyanum Diels et Gilg (TH), abbreviated as THP, is a water-soluble component extracted from TH, exhibiting anti-inflammatory and immunomodulatory properties. This study aims to investigate the effects and mechanisms of THP in sepsis. Results demonstrated that THP reduced neutrophils in the peripheral blood of mice established by cecal ligation and puncture (CLP), and inhibited IL-6 and MCP-1 in plasma, thereby improving systemic inflammation. THP ameliorated pulmonary edema, mitigated lung and liver histopathological injuries, reduced infiltration of neutrophils and macrophages in the lung and liver, and inhibited the TNF-α, IL-6, IL-1β, and MCP-1 transcription in both organs. Additionally, THP decreased myeloid cells, neutrophils, monocytes, and Tregs in the spleens of septic mice, while increasing T cells, CD4+ T cells, and CD8+ T cells, thereby restoring immune imbalance. Mechanistically, THP attenuated sepsis by inhibiting the overactivation of the TLR4/NF-κB/COX-2 pathway, and reducing PD-1, PD-L1, IDO1 in the lung, and PD-1, PD-L1 in the liver of septic mice. In conclusion, this study provides theoretical support for the potential application of THP in sepsis treatment.
{"title":"Alleviation of sepsis-induced lung and liver injury by polysaccharides from Tetrastigma hemsleyanum Diels et Gilg via suppression of TLR4/NF-κB/COX-2 pathway and modulation of immune checkpoint molecules","authors":"Mengjia Zhao ,&nbsp;Senmiao Chen ,&nbsp;Jingwen Xu ,&nbsp;Fangmei Zhou ,&nbsp;Mingyuan Zhou ,&nbsp;Shasha Tian ,&nbsp;Zhishan Ding ,&nbsp;Yuchi Chen","doi":"10.1016/j.molimm.2025.02.002","DOIUrl":"10.1016/j.molimm.2025.02.002","url":null,"abstract":"<div><div>Sepsis, a common clinical complication, leads to multi-organ damage due to systemic infection and currently lacks effective therapeutic drugs. Polysaccharide derived from <em>Tetrastigma hemsleyanum</em> Diels et Gilg (TH), abbreviated as THP, is a water-soluble component extracted from TH, exhibiting anti-inflammatory and immunomodulatory properties. This study aims to investigate the effects and mechanisms of THP in sepsis. Results demonstrated that THP reduced neutrophils in the peripheral blood of mice established by cecal ligation and puncture (CLP), and inhibited IL-6 and MCP-1 in plasma, thereby improving systemic inflammation. THP ameliorated pulmonary edema, mitigated lung and liver histopathological injuries, reduced infiltration of neutrophils and macrophages in the lung and liver, and inhibited the TNF-α, IL-6, IL-1β, and MCP-1 transcription in both organs. Additionally, THP decreased myeloid cells, neutrophils, monocytes, and Tregs in the spleens of septic mice, while increasing T cells, CD4<sup>+</sup> T cells, and CD8<sup>+</sup> T cells, thereby restoring immune imbalance. Mechanistically, THP attenuated sepsis by inhibiting the overactivation of the TLR4/NF-κB/COX-2 pathway, and reducing PD-1, PD-L1, IDO1 in the lung, and PD-1, PD-L1 in the liver of septic mice. In conclusion, this study provides theoretical support for the potential application of THP in sepsis treatment.</div></div>","PeriodicalId":18938,"journal":{"name":"Molecular immunology","volume":"179 ","pages":"Pages 52-64"},"PeriodicalIF":3.2,"publicationDate":"2025-02-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143316437","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
UBE2I depletion regulated tumor-associated macrophage polarization into M1 type through reprogramming glycolysis and increases immunotherapy efficacy of anti-PD-L1 in ovarian cancer
IF 3.2 3区 医学 Q2 BIOCHEMISTRY & MOLECULAR BIOLOGY Pub Date : 2025-02-06 DOI: 10.1016/j.molimm.2025.01.007
Lei Zhao , Yuxin Zhang , Jinming Wang, Dongliang Li, Xuewei Hao
There is ample evidence that ubiquitin-conjugating enzyme E2I (UBE2I) is involved in progression of diverse cancers. However, the influence of UBE2I on ovarian cancer (OC) has been poorly reported. This study tries to discover the mechanisms and functions of UBE2I in OC. Relative mRNA expression of UBE2I, CD86, iNOS, MHC II and programmed death ligand 1 (PD-L1) was detected through qRT-PCR. We identified UBE2I, Vimentin, E-Cadherin, N-Cadherin and Ki67 protein expression levels in tumor tissues through immunohistochemistry staining. Protein levels of UBE2I, cleaved caspase-3, cleaved PARP, E-cadherin, N-cadherin and Vimentin were detected through western blot. Cell viability, invasion, and migration were examined by means of cell counting kit-8 (CCK-8), transwell, and wound healing assays. Immunofluorescence was used to detect colocalization between UBE2I and CD68. We assessed expression levels of IFN-γ and TNF-α via flow cytometry and ELISA. We used the TUNEL assay to assess tumor cell apoptosis. Glycolysis was assessed through the consumption of glucose, ATP production, production of lactate, and extracellular acidification rate. For establishing a xenograft model, OC cells were subcutaneously injected into mice. UBE2I expression was boosted in OC cells and tissues, which was negatively associated with OC patients’ prognosis. Silencing of UBE2I suppressed OC cell proliferation, invasion, EMT (epithelial-to-mesenchymal transition) and migration. UBE2I inhibition promoted macrophages toward the M1 phenotype and macrophage viability. After deletion of UBE2I in vivo, mice tumor growth and EMT were suppressed, and apoptosis of tumor cells was increased. Meantime, an increasing proportion of CD86+ TAMs (tumor-associated macrophages) was observed after the deletion of UBE2I. Besides, increases in consumption of glucose, lactate production, ATP production and ECAR in THP-1 cells were observed by silencing of UBE2I; however, glycolysis inhibitor reversed UBE2I-mediated polarization of M1 macrophages in a dose-dependent fashion. Importantly, UBE2I-mediated M1 macrophages promoted PD-L1 expression. Furthermore, the combinatorial therapy of UBE2I inhibitor plus anti-PD-1 repressed tumor growth, reduced Ki67 expression, and promoted apoptosis in tumor cells, exhibiting higher efficiency than UBE2I inhibitor/anti-PD-L1 alone. UBE2I inhibition regulated polarization of M1 macrophages via glycolysis and improved anti-PD-L1 immunotherapy efficacy, paving a novel avenue to prevent OC development.
{"title":"UBE2I depletion regulated tumor-associated macrophage polarization into M1 type through reprogramming glycolysis and increases immunotherapy efficacy of anti-PD-L1 in ovarian cancer","authors":"Lei Zhao ,&nbsp;Yuxin Zhang ,&nbsp;Jinming Wang,&nbsp;Dongliang Li,&nbsp;Xuewei Hao","doi":"10.1016/j.molimm.2025.01.007","DOIUrl":"10.1016/j.molimm.2025.01.007","url":null,"abstract":"<div><div>There is ample evidence that ubiquitin-conjugating enzyme E2I (UBE2I) is involved in progression of diverse cancers. However, the influence of UBE2I on ovarian cancer (OC) has been poorly reported. This study tries to discover the mechanisms and functions of UBE2I in OC. Relative mRNA expression of UBE2I, CD86, iNOS, MHC II and programmed death ligand 1 (PD-L1) was detected through qRT-PCR. We identified UBE2I, Vimentin, E-Cadherin, N-Cadherin and Ki67 protein expression levels in tumor tissues through immunohistochemistry staining. Protein levels of UBE2I, cleaved caspase-3, cleaved PARP, E-cadherin, N-cadherin and Vimentin were detected through western blot. Cell viability, invasion, and migration were examined by means of cell counting kit-8 (CCK-8), transwell, and wound healing assays. Immunofluorescence was used to detect colocalization between UBE2I and CD68. We assessed expression levels of IFN-γ and TNF-α via flow cytometry and ELISA. We used the TUNEL assay to assess tumor cell apoptosis. Glycolysis was assessed through the consumption of glucose, ATP production, production of lactate, and extracellular acidification rate. For establishing a xenograft model, OC cells were subcutaneously injected into mice. UBE2I expression was boosted in OC cells and tissues, which was negatively associated with OC patients’ prognosis. Silencing of UBE2I suppressed OC cell proliferation, invasion, EMT (epithelial-to-mesenchymal transition) and migration. UBE2I inhibition promoted macrophages toward the M1 phenotype and macrophage viability. After deletion of UBE2I <em>in vivo</em>, mice tumor growth and EMT were suppressed, and apoptosis of tumor cells was increased. Meantime, an increasing proportion of CD86+ TAMs (tumor-associated macrophages) was observed after the deletion of UBE2I. Besides, increases in consumption of glucose, lactate production, ATP production and ECAR in THP-1 cells were observed by silencing of UBE2I; however, glycolysis inhibitor reversed UBE2I-mediated polarization of M1 macrophages in a dose-dependent fashion. Importantly, UBE2I-mediated M1 macrophages promoted PD-L1 expression. Furthermore, the combinatorial therapy of UBE2I inhibitor plus anti-PD-1 repressed tumor growth, reduced Ki67 expression, and promoted apoptosis in tumor cells, exhibiting higher efficiency than UBE2I inhibitor/anti-PD-L1 alone. UBE2I inhibition regulated polarization of M1 macrophages via glycolysis and improved anti-PD-L1 immunotherapy efficacy, paving a novel avenue to prevent OC development.</div></div>","PeriodicalId":18938,"journal":{"name":"Molecular immunology","volume":"179 ","pages":"Pages 29-41"},"PeriodicalIF":3.2,"publicationDate":"2025-02-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143316438","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Protective effect of Dendrobium officinale extract on aspirin-induced gastric lesions in rats
IF 3.2 3区 医学 Q2 BIOCHEMISTRY & MOLECULAR BIOLOGY Pub Date : 2025-02-06 DOI: 10.1016/j.molimm.2025.01.015
Xinran Wang , Huazhong Xiong , Juhui Qiao , Wanying Zhang , Siming Wang , Meichen Liu , Shichao Liu
To examine the protective effect and mechanism of the original extract of Dendrobium officinale (DE) on gastric lesions caused by aspirin (ASA) facilitate the development of traditional Chinese medicine products. In this study, a gastric lesions rat model was established, and then the rats were treated with DE for 5 days. We found that ASA-induced gastric mucosal detachment and hemorrhagic lesions in rats improved after DE supplementation. Meanwhile, effectively inhibits the secretion of inflammatory mediators (IL-6, IL-1β, TNF-α, MPO, COX-2) and upregulates the activity of antioxidant core components (T-SOD, GSH-Px) and defense factors (TFFs, EGF, EGFR) in gastric tissues. It was further found that DE exerted a defensive effect on the gastric mucosa in association with NF-κB/Nrf-2/HO-1 signaling. In conclusion, DE protects the gastric mucosa from oxidative stress, improves its defenses, as well as being a potential gastric mucosal nutrient in the future, preventing ASA-induced gastric lesions.
{"title":"Protective effect of Dendrobium officinale extract on aspirin-induced gastric lesions in rats","authors":"Xinran Wang ,&nbsp;Huazhong Xiong ,&nbsp;Juhui Qiao ,&nbsp;Wanying Zhang ,&nbsp;Siming Wang ,&nbsp;Meichen Liu ,&nbsp;Shichao Liu","doi":"10.1016/j.molimm.2025.01.015","DOIUrl":"10.1016/j.molimm.2025.01.015","url":null,"abstract":"<div><div>To examine the protective effect and mechanism of the original extract of <em>Dendrobium officinale</em> (DE) on gastric lesions caused by aspirin (ASA) facilitate the development of traditional Chinese medicine products. In this study, a gastric lesions rat model was established, and then the rats were treated with DE for 5 days. We found that ASA-induced gastric mucosal detachment and hemorrhagic lesions in rats improved after DE supplementation. Meanwhile, effectively inhibits the secretion of inflammatory mediators (IL-6, IL-1β, TNF-α, MPO, COX-2) and upregulates the activity of antioxidant core components (T-SOD, GSH-Px) and defense factors (TFFs, EGF, EGFR) in gastric tissues. It was further found that DE exerted a defensive effect on the gastric mucosa in association with NF-κB/Nrf-2/HO-1 signaling. In conclusion, DE protects the gastric mucosa from oxidative stress, improves its defenses, as well as being a potential gastric mucosal nutrient in the future, preventing ASA-induced gastric lesions.</div></div>","PeriodicalId":18938,"journal":{"name":"Molecular immunology","volume":"179 ","pages":"Pages 42-51"},"PeriodicalIF":3.2,"publicationDate":"2025-02-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143316436","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
SIRT3 mitigates neuroinflammation and mitochondrial damage post-hypoxic-ischemic brain injury
IF 3.2 3区 医学 Q2 BIOCHEMISTRY & MOLECULAR BIOLOGY Pub Date : 2025-02-05 DOI: 10.1016/j.molimm.2025.01.002
Ke Yan , Jiarong Bian , Liang He , Bingwei Song , Linhai Shen , Yong Zhen

Objective

We aimed to explore the role of SIRT3 in ameliorating neuroinflammation caused by hypoxia-ischemia (HI).

Methods

A rat model of HI was established, and 48 hours prior to constructing the HI model, the rats received an intracerebroventricular injection of a recombinant adeno-associated virus type 9 vector. TTC and Nissl staining assessed the effects of SIRT3 on cerebral infarction and brain atrophy in HI rats. Neuroinflammation was evaluated by investigating IL-1β and MPO positive cells, and ELISA for determining inflammatory cytokines. IBA-1, CD68, and iNOS positive microglia and NLRP3 activation-related protein expression were also detected. SIRT3 was overexpressed in oxygen glucose deprivation (OGD)-induced microglia model, where cell morphology and expressions of pro-inflammatory cytokines and NLRP3 inflammasome activation-related proteins were examined. Additionally, neurons co-cultured with SIRT3-overexpressing microglia were analyzed for mitochondrial damage and apoptosis.

Results

SIRT3 alleviated cerebral infarction and atrophy in HI rats. It also inhibited neuroinflammation, reducing IL-1β and MPO positive cells, and lowered the levels of pro-inflammatory cytokines. In both HI rat model and OGD cell model, SIRT3 inhibited excessive activation of microglia and NLRP3 inflammasome. Furthermore, co-culturing neurons with SIRT3-overexpressing microglia resulted in reduced neuronal apoptosis and improved mitochondrial function, evidenced by lower ROS levels, alleviated mitochondrial depolarization and increased ATP production.

Conclusion

SIRT3 restrains pro-inflammatory microglia and NLRP3 inflammasome and alleviates neuroinflammation following HI brain injury.
{"title":"SIRT3 mitigates neuroinflammation and mitochondrial damage post-hypoxic-ischemic brain injury","authors":"Ke Yan ,&nbsp;Jiarong Bian ,&nbsp;Liang He ,&nbsp;Bingwei Song ,&nbsp;Linhai Shen ,&nbsp;Yong Zhen","doi":"10.1016/j.molimm.2025.01.002","DOIUrl":"10.1016/j.molimm.2025.01.002","url":null,"abstract":"<div><h3>Objective</h3><div>We aimed to explore the role of SIRT3 in ameliorating neuroinflammation caused by hypoxia-ischemia (HI).</div></div><div><h3>Methods</h3><div>A rat model of HI was established, and 48 hours prior to constructing the HI model, the rats received an intracerebroventricular injection of a recombinant adeno-associated virus type 9 vector. TTC and Nissl staining assessed the effects of SIRT3 on cerebral infarction and brain atrophy in HI rats. Neuroinflammation was evaluated by investigating IL-1β and MPO positive cells, and ELISA for determining inflammatory cytokines. IBA-1, CD68, and iNOS positive microglia and NLRP3 activation-related protein expression were also detected. SIRT3 was overexpressed in oxygen glucose deprivation (OGD)-induced microglia model, where cell morphology and expressions of pro-inflammatory cytokines and NLRP3 inflammasome activation-related proteins were examined. Additionally, neurons co-cultured with SIRT3-overexpressing microglia were analyzed for mitochondrial damage and apoptosis.</div></div><div><h3>Results</h3><div>SIRT3 alleviated cerebral infarction and atrophy in HI rats. It also inhibited neuroinflammation, reducing IL-1β and MPO positive cells, and lowered the levels of pro-inflammatory cytokines. In both HI rat model and OGD cell model, SIRT3 inhibited excessive activation of microglia and NLRP3 inflammasome. Furthermore, co-culturing neurons with SIRT3-overexpressing microglia resulted in reduced neuronal apoptosis and improved mitochondrial function, evidenced by lower ROS levels, alleviated mitochondrial depolarization and increased ATP production.</div></div><div><h3>Conclusion</h3><div>SIRT3 restrains pro-inflammatory microglia and NLRP3 inflammasome and alleviates neuroinflammation following HI brain injury.</div></div>","PeriodicalId":18938,"journal":{"name":"Molecular immunology","volume":"179 ","pages":"Pages 18-28"},"PeriodicalIF":3.2,"publicationDate":"2025-02-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143315862","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Stigmasterol mitigates rheumatoid arthritis progression by decreasing Nrf2/NLRP3-mediated pyroptosis in chondrocyte
IF 3.2 3区 医学 Q2 BIOCHEMISTRY & MOLECULAR BIOLOGY Pub Date : 2025-02-04 DOI: 10.1016/j.molimm.2025.01.013
Li Ding , Huijun Lin , Zhidong Ma , Yong He , Sheng Ding , Kaile Zhang , Jiechao Zhang , Wenyao Li , Lianbo Xiao
Stigmasterol (Stig), a phytosterol with anti-inflammatory and antioxidant properties, has been shown to have potential therapeutic effects. In this study, we aimed to investigate whether Stig mitigates rheumatoid arthritis (RA) progression by reducing chondrocyte injury. A mouse model of RA was established by intradermally injecting type II collagen into the tail roots of mice. The arthritic score and spleen index were measured in RA mice to assess the effects of Stig on RA progression. Lipopolysaccharide (LPS)-treated chondrocytes were used as a cellular model of RA. The roles of Stig in chondrocyte viability, proliferation, migration, inflammation, and injury were assessed using Cell Counting Kit-8, EdU, Transwell assays, quantitative real-time PCR, and western blotting, respectively. The results demonstrated that Stig exhibited no significant cytotoxicity in CHON-001 chondrocytes. Interestingly, it effectively inhibited LPS-induced apoptosis and increased cell viability, proliferation, and migration. Stig also alleviated LPS-induced pro-inflammatory responses and CHON-001 cell injury. Mechanistically, Stig activated nuclear factor erythroid 2-related factor 2 (Nrf2) signaling, which led to the inactivation of the NOD-like receptor protein 3 (NLRP3) inflammasome and a subsequent decrease in CHON-001 cell pyroptosis. However, the protective effects of Stig were abrogated by ML385, a specific inhibitor Nrf2. Stig treatment further improved the clinical severity in RA mice. In summary, Stig reduces LPS-induced chondrocyte injury and mitigates RA progression by inhibiting Nrf2/NLRP3-mediated pyroptosis, offering a potential therapeutic approach for RA.
{"title":"Stigmasterol mitigates rheumatoid arthritis progression by decreasing Nrf2/NLRP3-mediated pyroptosis in chondrocyte","authors":"Li Ding ,&nbsp;Huijun Lin ,&nbsp;Zhidong Ma ,&nbsp;Yong He ,&nbsp;Sheng Ding ,&nbsp;Kaile Zhang ,&nbsp;Jiechao Zhang ,&nbsp;Wenyao Li ,&nbsp;Lianbo Xiao","doi":"10.1016/j.molimm.2025.01.013","DOIUrl":"10.1016/j.molimm.2025.01.013","url":null,"abstract":"<div><div>Stigmasterol (Stig), a phytosterol with anti-inflammatory and antioxidant properties, has been shown to have potential therapeutic effects. In this study, we aimed to investigate whether Stig mitigates rheumatoid arthritis (RA) progression by reducing chondrocyte injury. A mouse model of RA was established by intradermally injecting type II collagen into the tail roots of mice. The arthritic score and spleen index were measured in RA mice to assess the effects of Stig on RA progression. Lipopolysaccharide (LPS)-treated chondrocytes were used as a cellular model of RA. The roles of Stig in chondrocyte viability, proliferation, migration, inflammation, and injury were assessed using Cell Counting Kit-8, EdU, Transwell assays, quantitative real-time PCR, and western blotting, respectively. The results demonstrated that Stig exhibited no significant cytotoxicity in CHON-001 chondrocytes. Interestingly, it effectively inhibited LPS-induced apoptosis and increased cell viability, proliferation, and migration. Stig also alleviated LPS-induced pro-inflammatory responses and CHON-001 cell injury. Mechanistically, Stig activated nuclear factor erythroid 2-related factor 2 (Nrf2) signaling, which led to the inactivation of the NOD-like receptor protein 3 (NLRP3) inflammasome and a subsequent decrease in CHON-001 cell pyroptosis. However, the protective effects of Stig were abrogated by ML385, a specific inhibitor Nrf2. Stig treatment further improved the clinical severity in RA mice. In summary, Stig reduces LPS-induced chondrocyte injury and mitigates RA progression by inhibiting Nrf2/NLRP3-mediated pyroptosis, offering a potential therapeutic approach for RA.</div></div>","PeriodicalId":18938,"journal":{"name":"Molecular immunology","volume":"179 ","pages":"Pages 9-17"},"PeriodicalIF":3.2,"publicationDate":"2025-02-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143255856","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Esophageal squamous cell carcinoma derived sEV-PDL1 exhausts CD8+T cells to promote immunosuppression 食管鳞状细胞癌衍生的sEV-PDL1耗尽CD8+T细胞促进免疫抑制。
IF 3.2 3区 医学 Q2 BIOCHEMISTRY & MOLECULAR BIOLOGY Pub Date : 2025-02-01 DOI: 10.1016/j.molimm.2025.01.001
Zijie Li , Xiaokuan Zhang , Yuying Qi , Zhiyu Wang
Esophageal squamous cell carcinoma (ESCC) is a common malignancy. Programmed death ligand 1 of small extracellular vesicles (sEV-PDL1) induce immune evasion and enhance tumor progression. However, the role of ESCC derived sEV-PDL1 in modulating CD8+T cell remains unclear. sEVs were isolated through differential centrifugation. CD8+T cells were isolated, stimulated and cultured with sEVs to evaluate the proportions, phenotypes, and functions by flow cytometry. Lentivirus infection and Crisper-Cas9 were used to constructed stable transgenic cell lines: Eca109-PDL1kd and mEC25-PDL1ko. The proportions of CD8+T cells in ESCC patients was lower than healthy donors (HD). Furthermore, a negative correlation between sEV-PDL1 and CD8+T cell was observed. sEV-PDL1 induced CD8+T cell exhaustion by reducing the expression levels of Ki67, Granzyme B (GrzmB), and interferon-γ (IFN-γ) both in vitro and in vivo. However, anti-PDL1 reversed the result. Our findings reveal that targeting sEV-PDL1 to rejuvenate CD8+T cell functions is one of the mechnisms a promising therapeutic strategy for ESCC.
食管鳞状细胞癌(ESCC)是一种常见的恶性肿瘤。小细胞外囊泡中的程序性死亡配体1(sEV-PDL1)可诱导免疫逃避并促进肿瘤进展。然而,ESCC衍生的sEV-PDL1在调节CD8+T细胞方面的作用仍不清楚。用 sEVs 分离、刺激和培养 CD8+T 细胞,通过流式细胞术评估其比例、表型和功能。利用慢病毒感染和 Crisper-Cas9 技术构建了稳定的转基因细胞系:Eca109-PDL1kd和mEC25-PDL1ko。结果显示,ESCC患者的CD8+T细胞比例低于健康供体(HD)。此外,还观察到 sEV-PDL1 与 CD8+T 细胞呈负相关。sEV-PDL1 通过降低 Ki67、颗粒酶 B (GrzmB) 和干扰素-γ (IFN-γ) 在体外和体内的表达水平,诱导 CD8+T 细胞衰竭。然而,抗 PDL1 可逆转这一结果。我们的研究结果表明,靶向 sEV-PDL1 使 CD8+T 细胞功能恢复活力是一种很有前景的 ESCC 治疗策略。
{"title":"Esophageal squamous cell carcinoma derived sEV-PDL1 exhausts CD8+T cells to promote immunosuppression","authors":"Zijie Li ,&nbsp;Xiaokuan Zhang ,&nbsp;Yuying Qi ,&nbsp;Zhiyu Wang","doi":"10.1016/j.molimm.2025.01.001","DOIUrl":"10.1016/j.molimm.2025.01.001","url":null,"abstract":"<div><div>Esophageal squamous cell carcinoma (ESCC) is a common malignancy. Programmed death ligand 1 of small extracellular vesicles (sEV-PDL1) induce immune evasion and enhance tumor progression. However, the role of ESCC derived sEV-PDL1 in modulating CD8<sup>+</sup>T cell remains unclear. sEVs were isolated through differential centrifugation. CD8<sup>+</sup>T cells were isolated, stimulated and cultured with sEVs to evaluate the proportions, phenotypes, and functions by flow cytometry. Lentivirus infection and Crisper-Cas9 were used to constructed stable transgenic cell lines: Eca109-PDL1<sup>kd</sup> and mEC25-PDL1<sup>ko</sup>. The proportions of CD8<sup>+</sup>T cells in ESCC patients was lower than healthy donors (HD). Furthermore, a negative correlation between sEV-PDL1 and CD8<sup>+</sup>T cell was observed. sEV-PDL1 induced CD8<sup>+</sup>T cell exhaustion by reducing the expression levels of Ki67, Granzyme B (GrzmB), and interferon-γ (IFN-γ) both in vitro and in vivo. However, anti-PDL1 reversed the result. Our findings reveal that targeting sEV-PDL1 to rejuvenate CD8<sup>+</sup>T cell functions is one of the mechnisms a promising therapeutic strategy for ESCC.</div></div>","PeriodicalId":18938,"journal":{"name":"Molecular immunology","volume":"178 ","pages":"Pages 12-19"},"PeriodicalIF":3.2,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142971520","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Identification and characterization of the Cul t 1 as major allergen from biting midge Culicoides tainanus 台湾库蠓主要变应原cult1的鉴定与特征分析。
IF 3.2 3区 医学 Q2 BIOCHEMISTRY & MOLECULAR BIOLOGY Pub Date : 2025-02-01 DOI: 10.1016/j.molimm.2025.01.004
Shuncai Bao , Guangpeng Li , Xue Lu , Tengfei Lu , Xiaohui Hou

Background

Midges are widely distributed globally. They can transmit numerous serious diseases as well as trigger an allergic reaction in the host. Their saliva contains a variety of proteins that act as sensitizers to stimulate the host's immune response, leading to IgE-mediated allergic symptoms.

Material and method

In the present study, we constructed a mouse sensitization model with the thorax extract of the Culicoides tainanus, and evaluated the sensitization model by behavior and specific antibody expression. SDS-PAGE/western blot was used to detect the binding proteins by IgE antibody in the thorax extract of the C. tainanus. The objective band was cut for mass spectrometry to preliminarily clarify the potential allergen. The pET21a-Cul t 1 recombinant expression vector was constructed and the target protein was purified by Ni affinity chromatography. The sensitizing effect of the sensitizer was verified in vitro and in vivo.

Results

Immunoblot analysis revealed that a 66 kDa protein (Cul t 1) from the chest extracts of C. tainanus could bind to serum IgE of sensitized mice. Cul t 1 was further identified by fragmentation, mass spectrometry and bioinformatics as maltase, an enzyme involved in sugar digestion. In vivo validation of the Cul t 1-mouse sensitization model showed that the scratching behavior of the Cul t 1 sensitized group was significantly higher than that of the control group according to behavioral evaluation. The results of HE staining of the skin of the injected area showed that Cul t 1 sensitized group was found to have a large number of inflammatory cell infiltration and increased fibrosis in the dermis. The ELISA detection of IgE showed that the Cul t 1 sensitized group was significantly elevated from the beginning of the 28th day onwards, and the expression level of IgE had a tendency to slow down with the prolongation of the sensitization time. The ELISA assay showed that the expression level of IgG1 increased significantly in the Cul t 1 group on day 42, while the results of the specific antibody IgG2a showed that there was no significant difference in both the Cul t 1 sensitized group and the control group. The results suggest that the immune response induced by Cul t 1 sensitized mice may be shifted toward a Th2 type immune response.

Conclusions

In this study, we identified the sensitizer of the C. tainanus, named Cul t 1. We successfully constructed the recombinant expression vector pET21a-Cul t 1, purified the Cul t 1 sensitizer by affinity chromatography, and verified the sensitizing effect of Cul t 1 in mice. The results laid a practicable foundation for the subsequent immune therapy of midge bites and bite control.
背景:蠓在全球广泛分布。它们可以传播许多严重的疾病,并引发宿主的过敏反应。它们的唾液中含有多种蛋白质,这些蛋白质作为致敏剂刺激宿主的免疫反应,导致ige介导的过敏症状。材料与方法:本研究建立了鼠库蠓胸提取物致敏模型,并通过行为和特异性抗体表达评价模型的致敏效果。采用SDS-PAGE/western blot方法检测猪胸提取液中IgE抗体的结合蛋白。为初步查明潜在过敏原,对目标波段进行了质谱分析。构建pET21a-Cul t1重组表达载体,通过Ni亲和层析纯化目的蛋白。体外和体内实验验证了增敏剂的增敏效果。结果:免疫印迹分析显示,山参胸提物中66 kDa蛋白(Cul t1)可与致敏小鼠血清IgE结合。通过碎片化、质谱和生物信息学进一步鉴定cult1为麦芽糖酶,一种参与糖消化的酶。对Cul t1致敏小鼠模型进行体内验证,根据行为评价,Cul t1致敏组的抓痒行为显著高于对照组。注射区皮肤HE染色结果显示,Cul t1致敏组真皮内有大量炎性细胞浸润,纤维化增多。ELISA检测IgE结果显示,Cul t1致敏组从第28天开始显著升高,且随着致敏时间的延长,IgE表达水平有减慢的趋势。ELISA检测结果显示,Cul t1致敏组第42天IgG1表达水平显著升高,而特异性抗体IgG2a结果显示Cul t1致敏组与对照组无显著差异。结果提示cult1致敏小鼠的免疫反应可能向Th2型免疫反应转变。结论:在本研究中,我们鉴定了C. tainanus的致敏剂,命名为Cul t1。我们成功构建了重组表达载体pET21a-Cul t1,通过亲和层析纯化了Cul t1增敏剂,并在小鼠体内验证了Cul t1的增敏效果。研究结果为后续免疫治疗及蚊虫叮咬控制奠定了理论基础。
{"title":"Identification and characterization of the Cul t 1 as major allergen from biting midge Culicoides tainanus","authors":"Shuncai Bao ,&nbsp;Guangpeng Li ,&nbsp;Xue Lu ,&nbsp;Tengfei Lu ,&nbsp;Xiaohui Hou","doi":"10.1016/j.molimm.2025.01.004","DOIUrl":"10.1016/j.molimm.2025.01.004","url":null,"abstract":"<div><h3>Background</h3><div>Midges are widely distributed globally. They can transmit numerous serious diseases as well as trigger an allergic reaction in the host. Their saliva contains a variety of proteins that act as sensitizers to stimulate the host's immune response, leading to IgE-mediated allergic symptoms.</div></div><div><h3>Material and method</h3><div>In the present study, we constructed a mouse sensitization model with the thorax extract of the <em>Culicoides tainanus</em>, and evaluated the sensitization model by behavior and specific antibody expression. SDS-PAGE/western blot was used to detect the binding proteins by IgE antibody in the thorax extract of the <em>C. tainanus</em>. The objective band was cut for mass spectrometry to preliminarily clarify the potential allergen. The pET21a-<em>Cul t 1</em> recombinant expression vector was constructed and the target protein was purified by Ni affinity chromatography. The sensitizing effect of the sensitizer was verified <em>in vitro</em> and <em>in vivo</em>.</div></div><div><h3>Results</h3><div>Immunoblot analysis revealed that a 66 kDa protein (Cul t 1) from the chest extracts of <em>C. tainanus</em> could bind to serum IgE of sensitized mice. Cul t 1 was further identified by fragmentation, mass spectrometry and bioinformatics as maltase, an enzyme involved in sugar digestion. <em>In vivo</em> validation of the Cul t 1-mouse sensitization model showed that the scratching behavior of the Cul t 1 sensitized group was significantly higher than that of the control group according to behavioral evaluation. The results of HE staining of the skin of the injected area showed that Cul t 1 sensitized group was found to have a large number of inflammatory cell infiltration and increased fibrosis in the dermis. The ELISA detection of IgE showed that the Cul t 1 sensitized group was significantly elevated from the beginning of the 28th day onwards, and the expression level of IgE had a tendency to slow down with the prolongation of the sensitization time. The ELISA assay showed that the expression level of IgG1 increased significantly in the Cul t 1 group on day 42, while the results of the specific antibody IgG2a showed that there was no significant difference in both the Cul t 1 sensitized group and the control group. The results suggest that the immune response induced by Cul t 1 sensitized mice may be shifted toward a Th2 type immune response.</div></div><div><h3>Conclusions</h3><div>In this study, we identified the sensitizer of the <em>C. tainanus</em>, named Cul t 1. We successfully constructed the recombinant expression vector pET21a-<em>Cul t 1</em>, purified the Cul t 1 sensitizer by affinity chromatography, and verified the sensitizing effect of Cul t 1 in mice. The results laid a practicable foundation for the subsequent immune therapy of midge bites and bite control.</div></div>","PeriodicalId":18938,"journal":{"name":"Molecular immunology","volume":"178 ","pages":"Pages 32-40"},"PeriodicalIF":3.2,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143008718","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
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Molecular immunology
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