Central European Journal of Immunology最新文献

Introduction: Curcumin is a multi-functional component with anti-inflammatory and immunomodulatory properties. Unregulated immune responses may be a causative factor in the development of gestational diabetes mellitus (GDM). This study investigated the effect and mechanisms of curcumin on regulatory T cells/Th17 axis, and secretion of related cytokines (interleukin [IL]-17A, IL-6, and IL-10) in peripheral blood mononuclear cells (PBMCs) of healthy women and women with GDM.

Material and methods: This research involved in vitro experiments to evaluate the influence of curcumin on PBMCs; none of the subjects were taking any curcumin supplementation. Flow cytometry and ELISA were used in this study. Curcumin (1 μM, for 72 hours) treatment reduced the frequency of Th17 cells and the levels of related cytokines (IL-6, and IL-17) in women with GDM.

Results: The percentage of Th17 cells decreased after treatment with curcumin relative to untreated cells in the GDM group (p = 0.04). Curcumin reduced the IL-17A level in the GDM group (p = 0.01). Curcumin treatment reduced the IL-6 level only in the GDM group (p = 0.02). In the presence of curcumin, the IL-10 level in the supernatants of cell culture was significantly higher in the GDM group compared to the negative control (p = 0.0008).

Conclusions: The findings of the present study showed that curcumin modulated the immune responses via balancing of Treg/Th17 in women with GDM. Curcumin increased the level of IL-10, an anti-inflammatory cytokine, whereas it decreased the level of IL-6, which is related to the differentiation of Th17 cells. Curcumin treatment decreased the expression of IL-17A, the main secretory cytokine of Th17 cells. In conclusion, curcumin may act as an immunomodulator component in GDM by balancing the Th17/Treg axis.

Introduction: Rheumatoid arthritis (RA) is a chronic autoimmune disease that, if uncontrolled, leads to progressive joint damage. The potential immunomodulatory effects of COVID-19 vaccination on autoimmune disease activity remain an area of investigation.

Case report: We describe a 79-year-old woman with a 40-year history of RA, initially treated with methotrexate and, since 2008, with leflunomide (20 mg/day) in combination with corticosteroids (Urbason 8 mg/day) and non-steroidal anti-inflammatory drugs (NSAIDs). During the COVID-19 pandemic, after receiving three doses of the Pfizer vaccine, she discontinued leflunomide due to concerns about infection risk. Upon evaluation in 2021, despite residual joint damage in the hands, clinical and radiographic assessments confirmed inactive RA. Over a three-year follow-up, radiographs demonstrated stable erosions and osteopenic changes, corticosteroid therapy was progressively reduced, and anti-citrullinated protein antibody (ACPA) titers declined by approximately 50% compared to pre-vaccination levels.

Discussion and conclusions: This case suggests a potential immunologic "reset" following COVID-19 vaccination, contributing to sustained RA remission despite discontinuation of a conventional disease-modifying antirheumatic drug (DMARD). Although the precise mechanisms remain unclear, this observation aligns with emerging evidence that vaccine-induced immunomodulation may influence autoimmune disease activity. Further research, including larger controlled studies, is warranted to explore the potential benefits of COVID-19 vaccination in RA management.

Introduction: Inflammatory bowel disease (IBD) is a chronic and recurrent autoimmune condition. Numerous studies have reported that non-coding RNA, especially long non-coding RNA (lncRNA), plays a significant role in the regulation of IBD. This study sought to investigate the expression of lncRNA DDX11-antisense RNA 1 (DDX11-AS1) in IBD and its potential diagnostic value, while also evaluating the influence of DDX11-AS1 on the functionality of colorectal mucosal cells.

Material and methods: The expression trend of DDX11-AS1 was determined through PCR analysis, with its clinical diagnostic value assessed via ROC curve analysis. To construct an in vitro inflammation cell model, a commercially available human normal colon epithelial cell line (FHC) was selected and induced with lipopolysaccharide (LPS). Subsequently, the CCK-8 kit, flow cytometry, and ELISA were employed to assess cell viability, apoptosis, and inflammatory responses. The target gene miR-2355-5p of DDX11-AS1 was predicted using the Encyclopedia of RNA Interactomes (ENCORI), and the interaction relationship was validated by luciferase reporting assays.

Results: The study found that DDX11-AS1 expression is elevated, while miR-2355-5p expression is decreased, in patients with IBD. DDX11-AS1 demonstrated high diagnostic accuracy for IBD. In vitro, LPS exposure stimulated inflammation and apoptosis, and reduced cell viability in FHC cells. Downregulating DDX11-AS1 mitigated LPS-induced damage in these cells. Mechanistically, DDX11-AS1 was shown to directly target miR-2355-5p, exhibiting an inverse relationship.

Conclusions: The study findings suggest that the upregulation of DDX11-AS1 contributes to LPS- induced apoptosis and inflammation by targeting miR-2355-5p, offering new insights into the pathogenesis of IBD.

Introduction: Severe pneumonia in children is a rapidly progressing respiratory system disease. If not promptly controlled, it can lead to respiratory failure, posing a serious threat to the child's life. This study investigated the diagnostic and prognostic potential of miR-192-5p in children with severe pneumonia and respiratory failure.

Material and methods: A total of 62 children with severe pneumonia, 40 children with severe pneumonia and respiratory failure, and 62 healthy children were enrolled. The level of miR-192-5p was quantified by RT-qPCR assays. The diagnostic potential of miR-192-5p for severe pneumonia and respiratory failure was assessed through ROC curve and binary logistic analyses. The association between abnormal miR-192-5p level and prognosis of children with severe pneumonia with respiratory failure was evaluated by Kaplan-Meier and multivariate Cox analysis.

Results: miR-192-5p expression was decreased in the serum of severe pneumonia and expiratory failure children. miR-192-5p has a good potential to predict the occurrence of severe pneumonia, which is a risk predictor of severe pneumonia in children with respiratory failure. In addition, downregulation of miR-192-5p was strongly associated with poor prognosis of children with severe pneumonia and respiratory failure.

Conclusions: A low level of miR-192-5p has high predictive value and clinical development potential for the timely diagnosis and prediction of poor prognosis of children with severe pneumonia and respiratory failure.

Introduction: Excessive release of inflammatory cytokines in severe infections significantly contributes to the onset and progression of sepsis, a condition linked to elevated mortality rates in intensive care units. However, the lack of effective sepsis treatment strategies remains a significant challenge in critical care medicine. The use of anti-inflammatory agents against sepsis has advantages. Urinary trypsin inhibitor (UTI), a serine protease inhibitor obtained from the urine of healthy males, finds broad application in patients with inflammatory conditions such as shock, pancreatitis, and trauma. This investigation aimed to examine the impact and underlying mechanism of UTI in mice with sepsis and THP-1 cells stimulated by bacterial lipoprotein (BLP).

Material and methods: C57BL/6J mice were divided into the control, sham operation, cecal ligation and puncture (CLP), and UTI + CLP groups. Histological staining was performed to assess heart and lung injury. Transmission electron microscopy was performed to analyze myocardial mitochondrial injury. The creatine kinase-myoglobin binding and aspartate aminotransferase isoenzyme were detected by evaluating heart injury. Serum interleukin 1 β (IL-1 β) levels were identified using enzyme-linked immunosorbent assay. Human monocyte-derived THP-1 cells were cultured and divided into the control, BLP, and BLP + UTI (10, 100, 1000 U/ml, respectively) groups. Cell supernatant and extracted proteins from cultured cells treated at different UTI concentrations (10, 100, and 1000 U/ml) were collected to evaluate the tumor necrosis factor α (TNF-α) and IL-1 β levels using enzyme-linked immunosorbent assay. Western blot analysis was executed to evaluate the level of expression of nuclear factor kappa B (NF-κB), phosphorylated-I κB, I κB, phosphorylated protein 38, and protein 38.

Results: The CLP group exhibited elevated levels of creatine kinase-myoglobin binding, aspartate aminotransferase, and IL-1 β. However, after the administration of UTI, these levels decreased. UTI treatment proved effective in improving inflammatory injury in the heart and lung tissues in septic mice. Furthermore, it reduced the release of inflammatory cytokines in THP-1 cells stimulated by BLP. Additionally, treatment with UTI decreased the activity of NF-κB and upregulated the protein expression levels of phosphorylated-I κB and phosphorylated protein 38 in THP-1 cells induced by BLP.

Conclusions: UTI can effectively inhibit BLP-induced activation of the NF-κB/I κB and protein 38/mitogen-activated protein kinase signaling pathways, thereby suppressing the inflammatory response and improving sepsis.

Introduction: Growing evidence suggests that long non-coding RNA (lncRNA) GAS5 plays a critical role in inflammatory responses such as arthritis. In this study, we explored the function of GAS5 in acute gouty arthritis (AGA) and elucidated how GAS5 acts.

Material and methods: RT-qPCR was used to examine GAS5 expression levels in serum. Receiver operating characteristic (ROC) curve analysis was used to explore the diagnostic value of GAS5. The THP-1 cell model of AGA was established by monosodium urate (MSU) in vitro. The pro-inflammation cytokines interleukin (IL)-1 β, IL-8, and tumor necrosis factor α (TNF-α) were detected by enzyme-linked immunosorbent assay (ELISA). Bioinformatics analysis, correlation analysis, and dual luciferase reporter assay were performed for the target association between miR-485-5p and GAS5.

Results: GAS5 was suppressed in AGA patients, accompanied by upregulation of miR-485-5p. A high correlation between GAS5 and miR-485-5p was found, and GAS5 was associated with clinical characteristics in varying degrees. GAS5 achieved excellent performance accuracy, with the area under the ROC (AUC) of 0.915. Additionally, MSU-induced inflammatory responses were relieved through the overexpression of GAS5 in the cell model, while miR-485-5p overexpression reversed the responsiveness. The link between miR-485-5p and GAS5 was established in MSU-induced THP-1 macrophages.

Conclusions: In summary, GAS5 alleviated MSU-induced excessive inflammation in THP-1 macro- phages by targeting miR-485-5p, suggesting that GAS5 is a potential diagnostic biomarker for AGA treatment.

Introduction: Although the development of certain malignancies is linked to aberrant expression of LAMA1, it is not yet known how precisely LAMA1 regulates macrophage M2 polarization and the malignant evolution of colorectal cancer (CRC).

Material and methods: qRT-PCR and western blot (WB) were used to identify the expression of LAMA1 in human normal colonic epithelial cells (NCM-460) and CRC cell lines (RKO, LoVo). Using ELISA kits, the protein levels of LAMA1, interleukin (IL)-10, and Arg1 were determined. The assays used in the study included flow cytometry to evaluate CRC cell apoptosis and macrophage M2 polarization. Colony formation assessed the proliferative ability of co-cultured CRC cells, with Transwell assessing migration and invasion. WB identified the expression of proteins linked to the epithelial- mesenchymal transition (EMT).

Results: In CRC cells, LAMA1 was overexpressed. LAMA1 generated from CRC stimulated the EGFR/AKT/CREB signaling pathway in macrophages to induce M2 polarization of macrophages and eventually promote CRC cell proliferation, migration, and invasion, as well as to activate the EMT process and block CRC cell apoptosis.

Conclusions: As a pro-carcinogenic factor released by CRC cells, LAMA1 affects the activation of the EGFR/AKT/CREB pathway in macrophages, causing M2 polarization and aggravating the malignant evolution of CRC.

North-eastern Poland is an endemic region for tick-borne diseases, especially Lyme disease and tick-borne encephalitis. However, less common diseases such as rickettsiosis and tularemia may occur after a tick bite. In this paper we present a rare case of Rickettsia spp. and Francisella tularensis co-infection in a 46-year-old female patient with no history of travel and no chronic diseases, confirmed by serological and molecular tests. The symptoms appeared 5-7 days after the tick bite and lasted for 2 weeks. On physical examination, a maculopapular rash over the entire body, an ulcer on the left lower extremity, and an enlarged inguinal lymph node were noted. We concluded that rare diseases such as rickettsiosis and tularemia should be included in differential diagnosis of fever, lymphadenopathy and skin changes after a tick bite. Co-infection with Rickettsia spp. and F. tularensis is possible in patients after a tick bite. Quick diagnosis allows proper treatment (with doxycycline) and complete recovery.

Introduction: Macrophages are the primary cells of the mononuclear system. Studies have demonstrated that macrophages play an active role in the pathophysiology of cancers due to their remarkable adaptation capacities. The objective of this investigation was to examine the impact of apelin on macrophage polarization in the colon cancer microenvironment.

Material and methods: In this study, the colon adenocarcinoma cell line SW480 and mouse macro- phage cells RAW264.7 were used. Using shRNA, expression of the apelin gene was suppressed in SW480 cells. RAW264.7 cells were co-cultured with SW480 cells with the apelin gene silenced and no shRNA introduced. qRT-PCR and protein expression analysis were applied to assess the effect of apelin on inflammation-related genes and proteins, respectively, in co-cultured RAW264.7 cells.

Results: In comparison to the control, apelin knockdown led to significantly lower apelin expression in SW480 cells and a significant greater pro-inflammatory response in co-cultured macrophages. The expression levels of tumor necrosis factor αTNF-α, interleukin (IL)-6, and IL-1 genes were significantly elevated, while the amount of IL-10, which is known as an anti-inflammatory cytokine, was dramatically decreased. Pro-inflammatory genes, namely IL-1, IL-2 and TNF-α, were found to be downregulated, and anti-inflammatory genes, including IL-10 and transforming growth factor b (TGF-β, were found to be upregulated in the apelin-knockdown group compared to the control. Remarkably, the expression levels of IL-1, IL-6, and TNF-α proteins, which are involved in macrophage polarization, were in agreement with the qRT-PCR data.

Conclusions: These results indicate that the apelin peptide may be associated with the dense presence of M2-type macrophages in the cancer microenvironment, suggesting it as a therapeutic target for cancer cells.