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TNF-α/IL-1β/IL-1α/IL-12 inflammatory cytokine axes coupled with TLR1/TLR3/TLR5/MYD88 immune signaling pathway over-activation contribute to simultaneous carotid and coronary artery and occlusion in elderly patients TNF-α/IL-1β/IL-1α/IL-12炎症细胞因子轴与TLR1/TLR3/TLR5/MYD88免疫信号通路过度激活导致老年患者颈动脉和冠状动脉同时闭塞
IF 3.7 3区 医学 Q2 BIOCHEMISTRY & MOLECULAR BIOLOGY Pub Date : 2024-11-17 DOI: 10.1016/j.cyto.2024.156808
Wenhang Zhou , Xia Li , Hualan Zhou , Youdong Hu , Ying Chen , Dianxuan Guo

Background

It remains difficult to evaluate the risk factors for concomitant carotid artery as well as coronary artery diseases in elderly patients. The aim of this research was to determine the TNF-α/IL-1β/IL-1α/IL-12 axes-TLR1/TLR3/TLR5/MYD88 immune signaling pathway interactions in coexistent carotid artery occlusion and coronary artery occlusion in elderly patients.

Methods

Elderly patients, who underwent carotid ultrasonography and coronary computed tomography angiography, were consecutively included in this research. The analyzed groups consisted of those with coexistent carotid artery occlusion and coronary artery occlusion as well as healthy individuals were enrolled as control group. The circulating levels of tumor necrosis factor-α (TNF-α), interleukin-1β (IL-1β), interleukin-1α (IL-1α), interleukin-12 (IL-12), toll-like receptor 1 (TLR1), toll-like receptor 3 (TLR3), toll-like receptor 5 (TLR5) and myeloid differentiation factor 88 (MYD88) were measured.

Results

The biomarkers (TNF-α, IL-1β, IL-1α, IL-12, TLR1, TLR3, TLR5 and MYD88) were significantly increased in carotid artery occlusion + left circumflex coronary artery occlusion group when compared with control group and carotid artery occlusion + right coronary artery occlusion group, respectively (P < 0.001), and were further elevated in carotid artery occlusion + left anterior descending coronary artery occlusion group when compared to carotid artery occlusion + right coronary artery occlusion group and carotid artery occlusion + left circumflex coronary artery occlusion group, respectively (P < 0.001).

Conclusion

This research demonstrated that the TNF-α/IL-1β/IL-1α/IL-12 axes and TLR1/TLR3/TLR5/MYD88 immune signaling pathway implicated in the pathogenesis of carotid artery occlusion with coronary artery occlusion in elderly patients.
背景评估老年患者同时患有颈动脉和冠状动脉疾病的风险因素仍然很困难。本研究旨在确定 TNF-α/IL-1β/IL-1α/IL-12 轴-TLR1/TLR3/TLR5/MYD88 免疫信号通路在老年患者颈动脉闭塞和冠状动脉闭塞并存时的相互作用。分析组包括同时患有颈动脉闭塞和冠状动脉闭塞的患者,健康人作为对照组。研究人员测定了循环中肿瘤坏死因子-α(TNF-α)、白细胞介素-1β(IL-1β)、白细胞介素-1α(IL-1α)、白细胞介素-12(IL-12)、收费样受体1(TLR1)、收费样受体3(TLR3)、收费样受体5(TLR5)和髓样分化因子88(MYD88)的水平。结果 颈动脉闭塞+左侧冠状动脉闭塞组的生物标志物(TNF-α、IL-1β、IL-1α、IL-12、TLR1、TLR3、TLR5和MYD88)分别比对照组和颈动脉闭塞+右冠状动脉闭塞组明显升高(P < 0.001),颈动脉闭塞+左冠状动脉前降支闭塞组分别比颈动脉闭塞+右冠状动脉闭塞组和颈动脉闭塞+左冠状动脉环流闭塞组进一步升高(P < 0.001)。结论该研究表明,TNF-α/IL-1β/IL-1α/IL-12轴和TLR1/TLR3/TLR5/MYD88免疫信号通路与老年患者颈动脉闭塞合并冠状动脉闭塞的发病机制有关。
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引用次数: 0
The relationship between 25-hydroxyvitamin D and markers of intestinal and systemic inflammation in undernourished and non-undernourished children, 6–59 months 6-59 个月营养不良和非营养不良儿童体内 25- 羟维生素 D 与肠道和全身炎症指标之间的关系。
IF 3.7 3区 医学 Q2 BIOCHEMISTRY & MOLECULAR BIOLOGY Pub Date : 2024-11-16 DOI: 10.1016/j.cyto.2024.156807
Janet Adede Carboo, Linda Malan, Martani Lombard, Arista Nienaber, Robin Claire Dolman-Macleod

Background

Elevated inflammation contributes to growth faltering in children. Vitamin D (vitD) suppresses pro-inflammatory and enhances anti-inflammatory molecule production, thus vitamin D deficiency (VDD) has been associated with heightened inflammation. In undernourished children, VDD and inflammation co-exist, however, little is known about their interaction.

Objective

This cross-sectional study aimed to investigate the association of serum 25-hydroxyvitamin D (25(OH)D) concentration with markers of inflammation in undernourished and non-undernourished children, as well as the effect of vitD supplementation on inflammatory markers in the children with low 25(OH)D in a nested before-and-after trial.

Methods

Serum 25(OH)D, IL-1β, IL-8, IL-10, TNF-α, CRP, AGP, IFABP, sCD14, IGF-1 and FGF-21 of 121 undernourished and 51 non-undernourished children aged 6–59 months were measured cross-sectionally. Children with serum 25(OH)D < 30 ng/mL received 50,000 IU/week of vitD for three weeks.

Results

TNF-α and FGF-21 in the overall and undernourished group were higher in those with serum 25(OH)D < 30 ng/mL compared to those with serum ≥ 30 ng/mL (p < 0.05), while IFABP concentration was higher in the non-undernourished children with serum 25(OH)D < 30 ng/mL (p = 0.047). Serum 25(OH)D was negatively associated with TNF-α in the overall group (β = −0.012, p = 0.034); and FGF-21 (β = −0.013, p = 0.023) in the undernourished group. After the supplementation trial, TNF-α was reduced by 55.9 % (p = 0.008) and 64.7 % (p = 0.017) in the overall and undernourished groups respectively, and AGP showed a trend of 41.6 % reduction (p = 0.099) in the overall group. IL-1β concentration increased post-supplementation in the overall (p = 0.011) and undernourished groups (p = 0.039).

Conclusion

Optimising vitD status may potentially be a strategy for reducing systemic and gut inflammation, and subsequently improving growth, particularly in undernourished children.
背景:炎症加剧会导致儿童生长迟缓。维生素 D(vitD)可抑制促炎症反应,增强抗炎症分子的生成,因此维生素 D 缺乏症(VDD)与炎症反应加剧有关。在营养不良的儿童中,维生素 D 缺乏和炎症是并存的,但人们对它们之间的相互作用知之甚少:本横断面研究旨在调查营养不良儿童和非营养不良儿童血清 25- 羟基维生素 D(25(OH)D)浓度与炎症指标的关系,以及在嵌套前后试验中补充维生素 D 对低 25(OH)D 儿童炎症指标的影响:方法:横断面测量 121 名营养不良儿童和 51 名 6-59 个月非营养不良儿童的血清 25(OH)D、IL-1β、IL-8、IL-10、TNF-α、CRP、AGP、IFABP、sCD14、IGF-1 和 FGF-21。儿童的血清 25(OH)D 结果:有血清 25(OH)D 的儿童的 TNF-α 和 FGF-21 均高于营养不良的儿童:优化维生素 D 状态可能是减少全身和肠道炎症,进而改善生长状况的一种策略,尤其是在营养不良的儿童中。
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引用次数: 0
Antibody isotyping and cytokine profiling in natural cases of Burkholderia mallei infection (glanders) in equines 马伯克霍尔德氏菌感染(传染性单核细胞增多症)自然病例的抗体分型和细胞因子分析。
IF 3.7 3区 医学 Q2 BIOCHEMISTRY & MOLECULAR BIOLOGY Pub Date : 2024-11-16 DOI: 10.1016/j.cyto.2024.156799
Pooja , Naintara Thapa , Radha Rani , Karuppusamy Shanmugasundaram , Punit Jhandai , Rakshita , Tarun Kumar Bhattacharya , Harisankar Singha

Objectives

Immunological aspects of B. mallei infection were rarely studied in natural cases of equines. The present study was conducted to determine IgG, IgM, IgA and IgG (T) titre against recombinant Hcp1, TssA and TssB proteins and PilA-Hcp1-TssN-BipD and BpaB-BpaC- BMAA0553 chimeras and cytokine responses in glanders affected equine serum.

Methods

The study was conducted on serum samples collected from 151 glanders positive equines which include horses (n = 134), mules (n = 16), and donkeys (n = 01). The IgM, IgG, IgA and IgG (T) titre were determined against recombinant antigens by indirect ELISA and interleukin(IL)-1β, IL-17, IL-6, tumor necrosis factor alpha (TNF-α), monocyte chemoattractant protein 1 (MCP-1) and interferon gamma (IFN-γ) responses were measured by commercial ELISA kits.

Results

The study showed that glanders affected equines elicited strong antibody response against Hcp1, moderate responses against TssA and TssB, and weak responses against two chimeras. Among the cytokines, IL-1β, MCP-1, IL-17 and IL-6 concentration were significantly higher in glanders affected equine serum.

Conclusion

We found that IgG antibody titre was higher than IgM, IgG (T) and IgA isotypes and Hcp1 was most predominant antibody inducers in comparison to TssA, TssB, PilA-Hcp1-TssN-BipD and BpaB-BpaC-T2SS proteins. The elevated level of IL-1β, MCP-1, IL-17, IL-6, IFN-γ and TNF-α observed in this study support the important role of this cytokines for augmenting cellular defence by recruitment of macrophages, neutrophil and dendritic cells against B. mallei infection. Further studies should be conducted to determine memory cell responses in natural cases of equine glanders using recombinant B. mallei proteins for identifying well-characterized immuno-protective vaccine candidates.
目的:很少在马的自然病例中研究马雷杆菌感染的免疫学方面。本研究旨在确定受腺疽影响的马血清中针对重组 Hcp1、TssA 和 TssB 蛋白、PilA-Hcp1-TssN-BipD 和 BpaB-BpaC- BMAA0553 嵌合体的 IgG、IgM、IgA 和 IgG (T) 滴度以及细胞因子反应:研究对象为从 151 匹腺疽阳性马(包括马(n = 134)、骡(n = 16)和驴(n = 01))采集的血清样本。采用间接 ELISA 法测定重组抗原的 IgM、IgG、IgA 和 IgG (T) 滴度,采用商用 ELISA 试剂盒测定白细胞介素 (IL)-1β、IL-17、IL-6、肿瘤坏死因子α(TNF-α)、单核细胞趋化蛋白 1 (MCP-1) 和干扰素γ (IFN-γ) 反应:研究表明,传染性单核细胞增多症马对 Hcp1 产生强抗体反应,对 TssA 和 TssB 产生中度反应,对两种嵌合体产生弱反应。在细胞因子中,腺病马血清中 IL-1β、MCP-1、IL-17 和 IL-6 的浓度明显较高:结论:我们发现,IgG 抗体滴度高于 IgM、IgG (T) 和 IgA 同型,与 TssA、TssB、PilA-Hcp1-TssN-BipD 和 BpaB-BpaC-T2SS 蛋白相比,Hcp1 是最主要的抗体诱导物。本研究中观察到的 IL-1β、MCP-1、IL-17、IL-6、IFN-γ 和 TNF-α 水平的升高证明了这些细胞因子在通过招募巨噬细胞、中性粒细胞和树突状细胞来增强细胞防御功能以抵抗 B. mallei 感染方面的重要作用。应开展进一步研究,利用重组 B. mallei 蛋白确定马传染性单核细胞增多症自然病例中的记忆细胞反应,以确定特征明确的免疫保护性候选疫苗。
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引用次数: 0
Risk factors associated with short-term mortality in patients with candidemia and the predictive value of serum cytokine level 与念珠菌血症患者短期死亡率相关的风险因素及血清细胞因子水平的预测价值。
IF 3.7 3区 医学 Q2 BIOCHEMISTRY & MOLECULAR BIOLOGY Pub Date : 2024-11-15 DOI: 10.1016/j.cyto.2024.156803
Xueqing Fang , Congling Su , Yan Luo , Kai Pan , Jian Lin , Youliang Song , Yize Huang , Xiaochun Hu , Zhiyong Shen

Background

Some pro-inflammatory and anti-inflammatory cytokines were significantly elevated in patients with candidemia patients, but no studies have included these cytokines in the analysis of risk factors for mortality of candidemia. This study aims to analyze the risk factors of short-term mortality of candidemia and the predictive value of serum cytokines.

Methods

We retrospectively analyzed and compared the clinical features, risk factors and cytokine interleukin (IL)-6, interferon-γ (IFN-γ), IL-10 and IL-17 between survival group and death group in 53 patients with candidemia. Receiver operating of the characteristic curve (ROC) analysis was performed and figured up area under the curve (AUC), sensitivity and specificity values to assess the predictive power of independent factors associated with mortality.

Results

The overall in-hospital mortality rate of candidemia was 62.3 % (33/53), and the 30-day mortality rate was 52.8 % (28/53). The C. albicans accounting for 17.0 % (9/53), and the non-albicans Candida was 83.0 % (44/53). Serum IL-6 (p = 0.041, HR = 1.009), IFN-γ (p = 0.013, HR = 1.007, 95 %), procalcitonin (PCT) (p = 0.010, HR = 0.899) and Candida score (p = 0.033, HR = 1.659) were independent risk factors, while Initiation of targeted antifungal therapy within 48 h of positive blood cultures (BC) (P = 0.015, HR = 0.266) was a protective factor. The AUC of ROC for Candida score, serum IL-6, PCT, IFN-γ, and Initiation of targeted antifungal therapy within 48 h of positive BC showed 0.933, 0.841, 0.801, 0.732, 0.714, respectively. IL-6 and IFN-γ comprised good performing model for predicting 30-day and 90-day mortality, while IL-6 and IL-10 were the best combinations for predicting 90-day mortality.

Conclusions

Serum IL-6, IFN-γ, PCT, and Candida score can predict short-term mortality risk in patients with candidemia, while prompt and targeted antifungal treatment may reduce mortality. IL-6 could serve as a possible biomarker for predicting short-term mortality of candidemia and its combination with IL-10 or IFN-γ may further improve the predictive value.
背景:一些促炎和抗炎细胞因子在念珠菌血症患者中明显升高,但还没有研究将这些细胞因子纳入念珠菌血症死亡率的风险因素分析中。本研究旨在分析念珠菌病短期死亡率的风险因素以及血清细胞因子的预测价值:我们回顾性分析并比较了 53 例念珠菌病患者的临床特征、风险因素以及白细胞介素(IL)-6、干扰素-γ(IFN-γ)、IL-10 和 IL-17 等细胞因子在生存组和死亡组之间的差异。结果显示,53 例念珠菌血症患者中,存活组与死亡组之间的干扰素-γ(IFN-γ,IL-6)、IL-10、IL-17的预测能力存在差异:念珠菌血症的总体院内死亡率为 62.3%(33/53),30 天死亡率为 52.8%(28/53)。白念珠菌占 17.0%(9/53),非白念珠菌占 83.0%(44/53)。血清 IL-6(p = 0.041,HR = 1.009)、IFN-γ(p = 0.013,HR = 1.007,95 %)、降钙素原(PCT)(p = 0.010,HR = 0.899)和念珠菌评分(p = 0.033,HR = 1.而在血培养(BC)阳性 48 小时内开始针对性抗真菌治疗(P = 0.015,HR = 0.266)则是一个保护因素。念珠菌评分、血清 IL-6、PCT、IFN-γ 和 BC 阳性 48 小时内开始抗真菌靶向治疗的 ROC AUC 分别为 0.933、0.841、0.801、0.732、0.714。IL-6和IFN-γ是预测30天和90天死亡率的良好模型,而IL-6和IL-10是预测90天死亡率的最佳组合:结论:血清 IL-6、IFN-γ、PCT 和念珠菌评分可预测念珠菌血症患者的短期死亡风险,而及时、有针对性的抗真菌治疗可降低死亡率。IL-6可作为预测念珠菌血症短期死亡率的生物标志物,与IL-10或IFN-γ结合使用可进一步提高预测价值。
{"title":"Risk factors associated with short-term mortality in patients with candidemia and the predictive value of serum cytokine level","authors":"Xueqing Fang ,&nbsp;Congling Su ,&nbsp;Yan Luo ,&nbsp;Kai Pan ,&nbsp;Jian Lin ,&nbsp;Youliang Song ,&nbsp;Yize Huang ,&nbsp;Xiaochun Hu ,&nbsp;Zhiyong Shen","doi":"10.1016/j.cyto.2024.156803","DOIUrl":"10.1016/j.cyto.2024.156803","url":null,"abstract":"<div><h3>Background</h3><div>Some pro-inflammatory and anti-inflammatory cytokines were significantly elevated in patients with candidemia patients, but no studies have included these cytokines in the analysis of risk factors for mortality of candidemia. This study aims to analyze the risk factors of short-term mortality of candidemia and the predictive value of serum cytokines.</div></div><div><h3>Methods</h3><div>We retrospectively analyzed and compared the clinical features, risk factors and cytokine interleukin (IL)-6, interferon-γ (IFN-γ), IL-10 and IL-17 between survival group and death group in 53 patients with candidemia. Receiver operating of the characteristic curve (ROC) analysis was performed and figured up area under the curve (AUC), sensitivity and specificity values to assess the predictive power of independent factors associated with mortality.</div></div><div><h3>Results</h3><div>The overall in-hospital mortality rate of candidemia was 62.3 % (33/53), and the 30-day mortality rate was 52.8 % (28/53). The C. albicans accounting for 17.0 % (9/53), and the non-albicans Candida was 83.0 % (44/53). Serum IL-6 (p = 0.041, HR = 1.009), IFN-γ (p = 0.013, HR = 1.007, 95 %), procalcitonin (PCT) (p = 0.010, HR = 0.899) and Candida score (p = 0.033, HR = 1.659) were independent risk factors, while Initiation of targeted antifungal therapy within 48 h of positive blood cultures (BC) (P = 0.015, HR = 0.266) was a protective factor. The AUC of ROC for Candida score, serum IL-6, PCT, IFN-γ, and Initiation of targeted antifungal therapy within 48 h of positive BC showed 0.933, 0.841, 0.801, 0.732, 0.714, respectively. IL-6 and IFN-γ comprised good performing model for predicting 30-day and 90-day mortality, while IL-6 and IL-10 were the best combinations for predicting 90-day mortality.</div></div><div><h3>Conclusions</h3><div>Serum IL-6, IFN-γ, PCT, and Candida score can predict short-term mortality risk in patients with candidemia, while prompt and targeted antifungal treatment may reduce mortality. IL-6 could serve as a possible biomarker for predicting short-term mortality of candidemia and its combination with IL-10 or IFN-γ may further improve the predictive value.</div></div>","PeriodicalId":297,"journal":{"name":"Cytokine","volume":"185 ","pages":"Article 156803"},"PeriodicalIF":3.7,"publicationDate":"2024-11-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142637898","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
The multifunctional role of IFN-γ in Galleria mellonella (Lepidoptera) immunocompetent cells IFN-γ 在鳞翅目幼虫免疫细胞中的多功能作用
IF 3.7 3区 医学 Q2 BIOCHEMISTRY & MOLECULAR BIOLOGY Pub Date : 2024-11-15 DOI: 10.1016/j.cyto.2024.156804
Agata Kaczmarek, Anna Katarzyna Wrońska, Justyna Sobich, Mieczysława Irena Boguś
Cytokines are highly conserved between mammals and insects. The present study examines the multiple effects of interferon-gamma (IFN-γ) application on the immunological defence mechanisms of Galleria mellonella larvae, invertebrates which are gaining popularity as a replacement for mammalian research models in immunological studies. G. mellonella hemolymph is known to contain an IFN-γ homolog that shares 33 % similarity with its mammalian analogue, and its level in insect hemocytes increases during exposition to entomopathogenic fungus Conidiobolus coronatus. The present research examines the impact of IFN-γ on larval development, the effectiveness of fungal infection, and the morphology and physiology of wax moth immunocompetent cells. Treatment with IFN-γ enhanced wound healing, chemotaxis activity and hemocyte impedance, while reducing hemocyte phagocytosis and oxidative stress in cultured immunocompetent cells; it also appears to increase the levels of Jak-2- and NF-κB-like molecules in hemocytes. Our findings suggest that IFN-γ demonstrated considerable similarity between mammals and humans, thus further demonstrating the evolutionary conservatism of cytokines.
细胞因子在哺乳动物和昆虫之间高度保守。本研究探讨了干扰素-γ(IFN-γ)的应用对卵黑蝇幼虫免疫防御机制的多重影响,卵黑蝇幼虫是一种无脊椎动物,在免疫学研究中正逐渐成为哺乳动物研究模型的替代品。据了解,G. mellonella 血淋巴中含有一种 IFN-γ 同源物,与其哺乳动物类似物有 33% 的相似性,在昆虫暴露于昆虫病原真菌冠突散囊菌时,昆虫血细胞中的 IFN-γ 水平会升高。本研究探讨了 IFN-γ 对幼虫发育、真菌感染效果以及蜡蛾免疫细胞形态和生理的影响。用 IFN-γ 处理可增强伤口愈合、趋化活性和血细胞阻抗,同时降低血细胞吞噬能力和培养免疫活性细胞的氧化应激;它似乎还能提高血细胞中 Jak-2 和 NF-κB 类分子的水平。我们的研究结果表明,IFN-γ 在哺乳动物和人类之间表现出相当大的相似性,从而进一步证明了细胞因子的进化保守性。
{"title":"The multifunctional role of IFN-γ in Galleria mellonella (Lepidoptera) immunocompetent cells","authors":"Agata Kaczmarek,&nbsp;Anna Katarzyna Wrońska,&nbsp;Justyna Sobich,&nbsp;Mieczysława Irena Boguś","doi":"10.1016/j.cyto.2024.156804","DOIUrl":"10.1016/j.cyto.2024.156804","url":null,"abstract":"<div><div>Cytokines are highly conserved between mammals and insects. The present study examines the multiple effects of interferon-gamma (IFN-γ) application on the immunological defence mechanisms of <em>Galleria mellonella</em> larvae, invertebrates which are gaining popularity as a replacement for mammalian research models in immunological studies. <em>G. mellonella</em> hemolymph is known to contain an IFN-γ homolog that shares 33 % similarity with its mammalian analogue, and its level in insect hemocytes increases during exposition to entomopathogenic fungus <em>Conidiobolus coronatus</em>. The present research examines the impact of IFN-γ on larval development, the effectiveness of fungal infection, and the morphology and physiology of wax moth immunocompetent cells. Treatment with IFN-γ enhanced wound healing, chemotaxis activity and hemocyte impedance, while reducing hemocyte phagocytosis and oxidative stress in cultured immunocompetent cells; it also appears to increase the levels of Jak-2- and NF-κB-like molecules in hemocytes. Our findings suggest that IFN-γ demonstrated considerable similarity between mammals and humans, thus further demonstrating the evolutionary conservatism of cytokines.</div></div>","PeriodicalId":297,"journal":{"name":"Cytokine","volume":"185 ","pages":"Article 156804"},"PeriodicalIF":3.7,"publicationDate":"2024-11-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142637899","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
Hypercapnia promotes NLRP3 inflammasome activation in microglia by activating P2X7R after lipopolysaccharide-induced activation of the TLR4/NF-κB signaling pathway 在脂多糖诱导的TLR4/NF-κB信号通路激活后,高碳酸血症通过激活P2X7R促进小胶质细胞中NLRP3炎性体的激活。
IF 3.7 3区 医学 Q2 BIOCHEMISTRY & MOLECULAR BIOLOGY Pub Date : 2024-11-15 DOI: 10.1016/j.cyto.2024.156806
Hongguang Ding , Shiying Zhang , Zhuo Li , Juhao Zeng , Hongke Zeng

Background

Sepsis is an uncontrolled inflammatory response to infection and is closely associated with the occurrence of acute respiratory distress syndrome (ARDS). Low tidal volume lung ventilation and permissive hypercapnia is a recognized therapy for ARDS. However, whether permissive hypercapnia aggravates sepsis-associated encephalopathy (SAE) remains unclear. The present study investigated whether hypercapnia contributed to the development of SAE through the purinergic 2X7 receptor (P2X7R) by activating the Nod-like receptor protein 3 (NLRP3) inflammasome in sepsis.

Methods

The SAE model was established by intracranial injection of lipopolysaccharide (LPS) (1 μg/ml, 5 μl) in C57BL/6 mice. Hypercapnia was induced by mechanical ventilation with a high concentration of CO2 (5 % CO2, 21 % O2 and 74 % N2) in vivo. Toll-like receptor 4 (TLR4) and P2X7R knockout (KO) mice were employed in the study, while in vitro, BV2 microglial cells were treated with LPS or a high concentration of CO2 (15 % CO2 + 20 % O2). Immunofluorescence and western blot analysis were used to assess the expression levels of TLR4, NF-κB, phosphorylated (p)-NF-κB, P2X7R, pro-caspase-1, caspase-1, pro-IL-1β, IL-1β, pro-IL-18 and IL-18. ATP levels in the cell culture medium were detected by fluorometric assay.

Result

The results revealed that, compared with the sham group, the expression levels of TLR4, p-NF-κB, pro-IL-1β, pro-IL-18 and NLRP3 were significantly upregulated in the LPS and LPS + hypercapnia groups, but not in the hypercapnia group. Although the expression levels of caspase-1, IL-1β and IL-18 were increased slightly in the LPS group, their upregulation was more pronounced in the LPS + hypercapnia group, and it was suppressed when TLR4 was knocked out. Furthermore, P2X7R expression and ATP levels in the cell culture medium remained unchanged in the LPS group compared with the sham group but were remarkably increased both in the hypercapnia and LPS + hypercapnia groups. Additionally, P2X7R KO restrained the caspase-1, IL-1β and IL-18 increased induced by LPS injected intracranially and hypercapnia.

Conclusions

In conclusion, LPS induced the priming step of NLRP3 inflammasome activation, but had little effect on the activation step, while hypercapnia played an important role in the activation step through P2X7R, depending on the priming step stimulated by LPS.
背景:败血症是一种不受控制的感染炎症反应,与急性呼吸窘迫综合征(ARDS)的发生密切相关。低潮气量肺通气和允许性高碳酸血症是公认的 ARDS 治疗方法。然而,放任性高碳酸血症是否会加重脓毒症相关脑病(SAE)仍不清楚。本研究探讨了高碳酸血症是否会通过脓毒症患者的嘌呤能2X7受体(P2X7R)激活Nod样受体蛋白3(NLRP3)炎性体,从而导致SAE的发生:方法:通过向C57BL/6小鼠颅内注射脂多糖(LPS)(1 μg/ml,5 μl)建立SAE模型。通过高浓度二氧化碳(5 % CO2、21 % O2 和 74 % N2)机械通气诱导体内高碳酸血症。研究采用了Toll样受体4(TLR4)和P2X7R基因敲除(KO)小鼠,同时在体外用LPS或高浓度二氧化碳(15 % CO2 + 20 % O2)处理BV2小胶质细胞。免疫荧光和 Western 印迹分析用于评估 TLR4、NF-κB、磷酸化 (p)-NF-κB、P2X7R、pro-caspase-1、caspase-1、pro-IL-1β、IL-1β、pro-IL-18 和 IL-18 的表达水平。用荧光测定法检测细胞培养液中的 ATP 含量:结果显示:与假组相比,LPS 组和 LPS + 高碳酸血症组的 TLR4、p-NF-κB、pro-IL-1β、pro-IL-18 和 NLRP3 的表达水平明显升高,而高碳酸血症组则没有升高。虽然在 LPS 组中,caspase-1、IL-1β 和 IL-18 的表达水平略有升高,但在 LPS + 高碳酸血症组中,它们的上调更为明显,而当 TLR4 被敲除后,它们的上调被抑制。此外,与假组相比较,LPS 组细胞培养液中 P2X7R 的表达和 ATP 水平保持不变,但在高碳酸血症组和 LPS + 高碳酸血症组均显著增加。此外,P2X7R KO抑制了颅内注射LPS和高碳酸血症诱导的caspase-1、IL-1β和IL-18的增加:总之,LPS诱导了NLRP3炎症小体活化的启动步骤,但对活化步骤影响不大,而高碳酸血症则通过P2X7R在活化步骤中发挥重要作用,这取决于LPS刺激的启动步骤。
{"title":"Hypercapnia promotes NLRP3 inflammasome activation in microglia by activating P2X7R after lipopolysaccharide-induced activation of the TLR4/NF-κB signaling pathway","authors":"Hongguang Ding ,&nbsp;Shiying Zhang ,&nbsp;Zhuo Li ,&nbsp;Juhao Zeng ,&nbsp;Hongke Zeng","doi":"10.1016/j.cyto.2024.156806","DOIUrl":"10.1016/j.cyto.2024.156806","url":null,"abstract":"<div><h3>Background</h3><div>Sepsis is an uncontrolled inflammatory response to infection and is closely associated with the occurrence of acute respiratory distress syndrome (ARDS). Low tidal volume lung ventilation and permissive hypercapnia is a recognized therapy for ARDS. However, whether permissive hypercapnia aggravates sepsis-associated encephalopathy (SAE) remains unclear. The present study investigated whether hypercapnia contributed to the development of SAE through the purinergic 2X7 receptor (P2X7R) by activating the Nod-like receptor protein 3 (NLRP3) inflammasome in sepsis.</div></div><div><h3>Methods</h3><div>The SAE model was established by intracranial injection of lipopolysaccharide (LPS) (1 μg/ml, 5 μl) in C57BL/6 mice. Hypercapnia was induced by mechanical ventilation with a high concentration of CO<sub>2</sub> (5 % CO<sub>2</sub>, 21 % O<sub>2</sub> and 74 % N<sub>2</sub>) <em>in vivo</em>. Toll-like receptor 4 (TLR4) and P2X7R knockout (KO) mice were employed in the study, while <em>in vitro</em>, BV2 microglial cells were treated with LPS or a high concentration of CO<sub>2</sub> (15 % CO<sub>2</sub> + 20 % O<sub>2</sub>). Immunofluorescence and western blot analysis were used to assess the expression levels of TLR4, NF-κB, phosphorylated (p)-NF-κB, P2X7R, pro-caspase-1, caspase-1, pro-IL-1β, IL-1β, pro-IL-18 and IL-18. ATP levels in the cell culture medium were detected by fluorometric assay.</div></div><div><h3>Result</h3><div>The results revealed that, compared with the sham group, the expression levels of TLR4, p-NF-κB, pro-IL-1β, pro-IL-18 and NLRP3 were significantly upregulated in the LPS and LPS + hypercapnia groups, but not in the hypercapnia group. Although the expression levels of caspase-1, IL-1β and IL-18 were increased slightly in the LPS group, their upregulation was more pronounced in the LPS + hypercapnia group, and it was suppressed when TLR4 was knocked out. Furthermore, P2X7R expression and ATP levels in the cell culture medium remained unchanged in the LPS group compared with the sham group but were remarkably increased both in the hypercapnia and LPS + hypercapnia groups. Additionally, P2X7R KO restrained the caspase-1, IL-1β and IL-18 increased induced by LPS injected intracranially and hypercapnia.</div></div><div><h3>Conclusions</h3><div>In conclusion, LPS induced the priming step of NLRP3 inflammasome activation, but had little effect on the activation step, while hypercapnia played an important role in the activation step through P2X7R, depending on the priming step stimulated by LPS.</div></div>","PeriodicalId":297,"journal":{"name":"Cytokine","volume":"185 ","pages":"Article 156806"},"PeriodicalIF":3.7,"publicationDate":"2024-11-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142643603","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
Exploring the innate immune response in polycystic liver disease 探索多囊肝病的先天免疫反应。
IF 3.7 3区 医学 Q2 BIOCHEMISTRY & MOLECULAR BIOLOGY Pub Date : 2024-11-13 DOI: 10.1016/j.cyto.2024.156800
Renée Duijzer , Daisy Dalloyaux , Melissa M. Boerrigter , Heidi Lemmers , Helga Dijkstra , Liesbeth van Emst , René H.M. te Morsche , Martin Jaeger , Leo A.B. Joosten , Joost P.H. Drenth

Rationale

The role of the innate immune system in polycystic liver disease (PLD) has been underexplored despite its potential importance in disease progression. This study explores the innate immune response in PLD patients by analyzing cytokine production of peripheral blood mononuclear cells (PBMCs) in response to various pathogens compared to healthy controls.

Methods

Samples were collected from patients with ADPLD or ADPKD and PLD. PBMCs were isolated and stimulated with LPS (1 ng), LPS (10 ng), E. coli, K. pneumoniae, S. aureus, and C. albicans. ELISA was used to measure TNF, IL-1β, IL-1Ra, IL-6, and IL-8 concentrations after 24 hours, and IL-17, IL-22, and IFNγ concentrations after 7 days. Control samples were matched for age and gender.

Results

104 patients and 12 controls were included. PLD patients showed consistent increased IL-6 concentrations compared to controls. Other cytokine levels varied per stimulus. Controls showed higher IL-8 and TNF concentrations in response to Gram-negative bacteria, while PLD patients showed higher IL-1β and IL-1Ra levels in response to S. aureus and C. albicans. No clear differences were found in IL-17, IL-22, and IFN-γ concentrations after 7 days. These observed differences were independent of demographic and clinical parameters.

Conclusion

Compared to healthy controls, the PLD patients innate immune system shows an altered response when stimulated by various pathogens. These findings underscore the importance of further investigation into the underlying mechanisms as this might help our understanding disease progression and be a potential target for new therapies.
理由:先天性免疫系统在多囊性肝病(PLD)中的作用尽管在疾病进展中具有潜在的重要性,但一直未得到充分探索。本研究通过分析外周血单核细胞(PBMCs)与健康对照组相比在应对各种病原体时产生的细胞因子,探讨多囊肝病患者的先天性免疫反应:方法:采集 ADPLD 或 ADPKD 合并 PLD 患者的样本。方法:从 ADPLD 或 ADPKD 和 PLD 患者身上采集样本,分离 PBMC,用 LPS(1 毫微克)、LPS(10 毫微克)、大肠杆菌、肺炎双球菌、金黄色葡萄球菌和白僵菌刺激 PBMC。用酶联免疫吸附法测定 24 小时后 TNF、IL-1β、IL-1Ra、IL-6 和 IL-8 的浓度,以及 7 天后 IL-17、IL-22 和 IFNγ 的浓度。对照组样本的年龄和性别均匹配:结果:共纳入 104 例患者和 12 例对照组样本。与对照组相比,PLD 患者的 IL-6 浓度持续升高。其他细胞因子水平因刺激而异。对照组对革兰氏阴性菌反应的 IL-8 和 TNF 浓度较高,而 PLD 患者对金黄色葡萄球菌和白色念球菌反应的 IL-1β 和 IL-1Ra 浓度较高。7天后,IL-17、IL-22和IFN-γ浓度没有明显差异。这些观察到的差异与人口统计学和临床参数无关:结论:与健康对照组相比,PLD 患者的先天性免疫系统在受到各种病原体刺激时表现出不同的反应。这些发现强调了进一步研究其潜在机制的重要性,因为这可能有助于我们了解疾病的进展,并成为新疗法的潜在靶点。
{"title":"Exploring the innate immune response in polycystic liver disease","authors":"Renée Duijzer ,&nbsp;Daisy Dalloyaux ,&nbsp;Melissa M. Boerrigter ,&nbsp;Heidi Lemmers ,&nbsp;Helga Dijkstra ,&nbsp;Liesbeth van Emst ,&nbsp;René H.M. te Morsche ,&nbsp;Martin Jaeger ,&nbsp;Leo A.B. Joosten ,&nbsp;Joost P.H. Drenth","doi":"10.1016/j.cyto.2024.156800","DOIUrl":"10.1016/j.cyto.2024.156800","url":null,"abstract":"<div><h3>Rationale</h3><div>The role of the innate immune system in polycystic liver disease (PLD) has been underexplored despite its potential importance in disease progression. This study explores the innate immune response in PLD patients by analyzing cytokine production of peripheral blood mononuclear cells (PBMCs) in response to various pathogens compared to healthy controls.</div></div><div><h3>Methods</h3><div>Samples were collected from patients with ADPLD or ADPKD and PLD. PBMCs were isolated and stimulated with LPS (1 ng), LPS (10 ng), <em>E. coli</em>, <em>K. pneumoniae</em>, <em>S. aureus</em>, and <em>C. albicans</em>. ELISA was used to measure TNF, IL-1β, IL-1Ra, IL-6, and IL-8 concentrations after 24 hours, and IL-17, IL-22, and IFNγ concentrations after 7 days. Control samples were matched for age and gender.</div></div><div><h3>Results</h3><div>104 patients and 12 controls were included. PLD patients showed consistent increased IL-6 concentrations compared to controls. Other cytokine levels varied per stimulus. Controls showed higher IL-8 and TNF concentrations in response to Gram-negative bacteria, while PLD patients showed higher IL-1β and IL-1Ra levels in response to <em>S. aureus</em> and <em>C. albicans</em>. No clear differences were found in IL-17, IL-22, and IFN-γ concentrations after 7 days. These observed differences were independent of demographic and clinical parameters.</div></div><div><h3>Conclusion</h3><div>Compared to healthy controls, the PLD patients innate immune system shows an altered response when stimulated by various pathogens. These findings underscore the importance of further investigation into the underlying mechanisms as this might help our understanding disease progression and be a potential target for new therapies.</div></div>","PeriodicalId":297,"journal":{"name":"Cytokine","volume":"184 ","pages":"Article 156800"},"PeriodicalIF":3.7,"publicationDate":"2024-11-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142610820","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
The cGAS-STING pathway as a novel therapeutic strategy for pancreatic diseases 将 cGAS-STING 通路作为胰腺疾病的新型治疗策略。
IF 3.7 3区 医学 Q2 BIOCHEMISTRY & MOLECULAR BIOLOGY Pub Date : 2024-11-10 DOI: 10.1016/j.cyto.2024.156801
Zhengda Pei , Mengxiang Tian
The Cyclic GMP-AMP synthase (cGAS)-Stimulator of interferon genes [1] signaling pathway has emerged as a pivotal immune response mechanism, activating immune defenses upon detection of both exogenous and endogenous DNA within cells. Its activation is intricately linked to various diseases and inflammatory processes, spanning autoimmune disorders, infectious ailments, and malignancies. Among pancreatic diseases, encompassing acute pancreatitis, chronic pancreatitis, and pancreatic cancer, current clinical treatment efficacy remains suboptimal. Here, we elucidate the molecular intricacies of the cGAS-STING signaling pathway and delineate its therapeutic potential in acute pancreatitis, chronic pancreatitis, and pancreatic cancer. Additionally, we offer an overview of recent advancements in STING agonists and antagonists, assessing their therapeutic potential in pancreatic-related disorders. In summary, by exploring the multifaceted roles of the cGAS-STING signaling pathway and its implications in pancreatic diseases, we aim to shed light on potential avenues for therapeutic intervention and management in these challenging clinical contexts.
环状 GMP-AMP 合成酶(cGAS)-干扰素基因刺激器[1]信号通路已成为一种关键的免疫反应机制,在检测到细胞内的外源性和内源性 DNA 时激活免疫防御机制。它的激活与各种疾病和炎症过程密切相关,包括自身免疫性疾病、传染性疾病和恶性肿瘤。在包括急性胰腺炎、慢性胰腺炎和胰腺癌在内的胰腺疾病中,目前的临床治疗效果仍不理想。在此,我们阐明了 cGAS-STING 信号通路的分子复杂性,并描述了其在急性胰腺炎、慢性胰腺炎和胰腺癌中的治疗潜力。此外,我们还概述了 STING 激动剂和拮抗剂的最新进展,评估了它们在胰腺相关疾病中的治疗潜力。总之,通过探索 cGAS-STING 信号通路的多方面作用及其在胰腺疾病中的影响,我们旨在阐明在这些具有挑战性的临床环境中进行治疗干预和管理的潜在途径。
{"title":"The cGAS-STING pathway as a novel therapeutic strategy for pancreatic diseases","authors":"Zhengda Pei ,&nbsp;Mengxiang Tian","doi":"10.1016/j.cyto.2024.156801","DOIUrl":"10.1016/j.cyto.2024.156801","url":null,"abstract":"<div><div>The Cyclic GMP-AMP synthase (cGAS)-Stimulator of interferon genes <span><span>[1]</span></span> signaling pathway has emerged as a pivotal immune response mechanism, activating immune defenses upon detection of both exogenous and endogenous DNA within cells. Its activation is intricately linked to various diseases and inflammatory processes, spanning autoimmune disorders, infectious ailments, and malignancies. Among pancreatic diseases, encompassing acute pancreatitis, chronic pancreatitis, and pancreatic cancer, current clinical treatment efficacy remains suboptimal. Here, we elucidate the molecular intricacies of the cGAS-STING signaling pathway and delineate its therapeutic potential in acute pancreatitis, chronic pancreatitis, and pancreatic cancer. Additionally, we offer an overview of recent advancements in STING agonists and antagonists, assessing their therapeutic potential in pancreatic-related disorders. In summary, by exploring the multifaceted roles of the cGAS-STING signaling pathway and its implications in pancreatic diseases, we aim to shed light on potential avenues for therapeutic intervention and management in these challenging clinical contexts.</div></div>","PeriodicalId":297,"journal":{"name":"Cytokine","volume":"184 ","pages":"Article 156801"},"PeriodicalIF":3.7,"publicationDate":"2024-11-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142610821","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
Interleukin 17 producing T cell responses in human chronic trichinellosis-insight from a case study 人类慢性旋毛虫病中产生白细胞介素 17 的 T 细胞反应--一项病例研究的启示。
IF 3.7 3区 医学 Q2 BIOCHEMISTRY & MOLECULAR BIOLOGY Pub Date : 2024-11-03 DOI: 10.1016/j.cyto.2024.156795
Chiara Della Bella , Chiara Medici , Sofia D’Elios , Marisa Benagiano , Alessandra Ludovisi , Maria Angeles Gomez-Morales , Mario M. D’Elios , Fabrizio Bruschi

Introduction

We studied the cellular immune response in a patient infected since 10 months (along with other 51 people) during a trichinellosis outbreak caused by Trichinella spp.

Methods

A 46 years old female resulted serologically positive for trichinellosis. We isolated peripheral blood mononuclear cells (PBMCs) and incubated them with excretory/secretory antigens (ESA) of Trichinella spiralis (T1) or Trichinella pseudospiralis (T4) to produce antigen specific T cell lines and clones, analysed for the phenotype (T helper or cytotoxic cells), for their T4 or T1 antigens specificity and for their cytokine profile (IFNγ, IL-17A, IL-4) by flow cytometry, thymidine incorporation assay and ELISpot.

Results

The test performed using ESA from T1 or T4 has identified the species responsible for infection as T. pseudospiralis since the proliferative responses (evaluated by CFSE, Carboxyfluorescein succinimidyl ester, FACS analysis) was higher for T4 (72,8%) than T1 (23.6 %) antigen. The cell lines produced significant levels of IFNγ, IL-4 and IL-17A after stimulation. From the T cell line obtained in response to T1 ESA, as regards CD4 + cells, 12 % Th2, 22.8 % Th1, 6.6 % Th17, 6 % Th0, 2.2 % Th1/Th17 and 0.7 % Th2/Th17, were obtained. From the T1-specific TCL we generated 15 clones. From the TCL specific for T4 ESA, as regards CD4+, 15.2 % Th2, 27.1 % Th1, 3 % Th17, 10.3 %Th0, 1.9 % Th1/Th17 and 1 % Th2/ Th17 were obtained. From such TCL 4 clones were isolated, 1Th2, 1 Th1, 1 Th17, 1 Th1/Th17 and no Th0 nor Th2/Th17.

Conclusions

By cellular immunology techniques the species responsible of the infection resulted T. pseudospiralis, confirming the results previously obtained by serology. For the first time it was revealed in a human chronic infection the presence of Th17 cells.
简介:我们研究了一名在由旋毛虫引起的旋毛虫病暴发中感染了 10 个月(以及其他 51 人)的患者的细胞免疫反应:我们研究了一名在由旋毛虫引起的旋毛虫病爆发期间感染了 10 个月的患者(以及其他 51 人)的细胞免疫反应:一名 46 岁女性的毛霉菌病血清学检测结果呈阳性。我们分离了外周血单核细胞(PBMCs),并将其与螺旋毛癣菌(T1)或假螺旋毛癣菌(T4)的排泄/分泌抗原(ESA)培养,以产生抗原特异性 T 细胞系和克隆、通过流式细胞术、胸腺嘧啶掺入试验和 ELISpot 分析表型(T 辅助细胞或细胞毒性细胞)、T4 或 T1 抗原特异性及其细胞因子谱(IFNγ、IL-17A、IL-4)。结果:使用 T1 或 T4 的 ESA 进行的检测确定了造成感染的物种为假丝酵母菌,因为 T4(72.8%)的增殖反应(通过 CFSE、羧基荧光素琥珀酰亚胺酯和 FACS 分析评估)高于 T1(23.6%)抗原。细胞系在受到刺激后会产生大量的 IFNγ、IL-4 和 IL-17A。从对 T1 ESA 有反应的 T 细胞系中获得的 CD4 + 细胞中,Th2 细胞占 12%,Th1 细胞占 22.8%,Th17 细胞占 6.6%,Th0 细胞占 6%,Th1/Th17 细胞占 2.2%,Th2/Th17 细胞占 0.7%。我们从 T1 特异性 TCL 中产生了 15 个克隆。从 T4 ESA 特异性 TCL 中获得了 15.2 % Th2、27.1 % Th1、3 % Th17、10.3 %Th0、1.9 % Th1/Th17 和 1 % Th2/Th17。从这些 TCL 中分离出 4 个克隆,1 个 Th2、1 个 Th1、1 个 Th17、1 个 Th1/Th17,没有 Th0 或 Th2/Th17:通过细胞免疫学技术,导致感染的物种是伪螺旋体,这证实了之前通过血清学获得的结果。在人类慢性感染中首次发现了 Th17 细胞的存在。
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引用次数: 0
Diphencyprone reduces the CD8+ lymphocytes and IL-4 and enhences IgG2a/IgG1 ratio in pathogenicity of acute leishmania major infection in BALB/c mice 在 BALB/c 小鼠急性利什曼原虫感染的致病性过程中,地芬诺酯可减少 CD8+ 淋巴细胞和 IL-4,并提高 IgG2a/IgG1 比率。
IF 3.7 3区 医学 Q2 BIOCHEMISTRY & MOLECULAR BIOLOGY Pub Date : 2024-11-02 DOI: 10.1016/j.cyto.2024.156792
Pourandokht Mousavian , Vahid Mashayekhi Goyonlo , Mohammad Javanbakht , Mahmoud Reza Jafari , Hamidreza Moosavian , Monovar Afzal Aghaei , Mohammadreza Malekzadeh

Background

The exact role of different immune cells and cytokines in control or promotion of intracellular growth of leishmania has still remained a controversial topic. The aim of the present study was to study effects of cellular changes and relevant cytokines in cell mediated immunity by diphencyprone (DCP) in pathogenicity of acute L.major infection in BALB/c mice.

Methods

45 healthy female BALB/c mice were injected with L. major promastigotes under the base of tail. The mice were randomly divided to three groups of 15 mice: (1) control group without any treatment. (2) acetone group: Acetone was applied topically on the cutaneous lesions weekly and (3) DCP group: DCP was applied topically on the cutaneous lesions with increasing concentrations to induce local allergy. The mice were followed by the end of eighth week, and then macroscopic changes, histopathology, immunology studies, and organ parasite burden were determined.

Results

In DCP group, in comparison to other groups the ulcer size and parasite burden in ulcer site and spleen increased, significantly. There was a deep lymphohistiocytic infiltration in the ulcer site. Total IgG, IgG1, and IgG2a levels as well as IgG2a/IgG1 ratio and intracellular IFN-gamma in CD8+ lymphocytes were significantly higher. IL4 and T CD8+ lymphocytes were significantly lower in DCP group. The IgG2a/IgG1 ratio was more than 1 in all groups.

Conclusion

Our findings demonstrated that DCP reduced the CD8+ lymphocytes and IL-4 production. In spite of increased IgG2a/IgG1 ratio, the parasite burden and inflammation severity increased in infected mice. The results can show the pivotal role of CD8+ lymphocytes in conjunction with Th1 lymphocytes in the control of acute leishmania infection in mice.
背景:不同的免疫细胞和细胞因子在控制或促进利什曼原虫细胞内生长中的确切作用仍是一个有争议的话题。本研究的目的是研究二苯基丙酮(DCP)对 BALB/c 小鼠急性利什曼原虫感染致病性的细胞变化和细胞介导免疫中相关细胞因子的影响。将小鼠随机分为三组,每组 15 只:(1)对照组,不做任何处理。(2)丙酮组:每周将丙酮局部涂抹在皮肤病变处;(3) DCP 组:在小鼠皮损处局部涂抹二氯丙醇,浓度不断增加,以诱发局部过敏。第八周结束时对小鼠进行随访,然后测定小鼠的宏观变化、组织病理学、免疫学研究和器官寄生虫负荷:结果:与其他组相比,DCP 组的溃疡面积和溃疡部位及脾脏的寄生虫量明显增加。溃疡部位有深层淋巴组织细胞浸润。总 IgG、IgG1 和 IgG2a 水平以及 IgG2a/IgG1 比率和 CD8+ 淋巴细胞内的 IFN-gamma 均明显升高。DCP组的IL4和T CD8+淋巴细胞明显降低。所有组的 IgG2a/IgG1 比值均大于 1:我们的研究结果表明,DCP 减少了 CD8+ 淋巴细胞和 IL-4 的产生。结论:我们的研究结果表明,DCP 减少了 CD8+ 淋巴细胞和 IL-4 的产生,尽管 IgG2a/IgG1 比率增加,但感染小鼠的寄生虫负荷和炎症严重程度却增加了。这些结果表明,CD8+淋巴细胞与 Th1 淋巴细胞一起在控制小鼠急性利什曼病感染中发挥着关键作用。
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引用次数: 0
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Cytokine
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