Central European Journal of Immunology最新文献

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.

Introduction: The present study aimed to investigate the involvement of microfibril-associated protein 2 (MFAP2), a multifunctional secreted protein and constituent of extracellular matrix microfibrils, in the tumorigenicity of uterine corpus endometrial carcinoma (UCEC).

Material and methods: The mRNA expression levels of MFAP2A were detected in a total of 52 pairs of UCEC and adjacent non-tumorous tissues. Cell proliferation, migration and invasion, as well as cell apoptosis, were assessed using CCK8, Transwell and TUNEL assays, respectively. In addition, overall survival, Gene Ontology and Kyoto Encyclopedia of Genes and Genomes enrichment and gene alterations were determined by bioinformatic analysis.

Results: The results showed that MFAP2 and transcription factor 7 like 1 (TCF7L1) were significantly upregulated in UCEC tissues compared with normal non-tumoral tissues. Also, a notable positive association between MFAP2 and TCF7L1 was observed in UCEC tissues. Furthermore, MFAP2 silencing notably attenuated the proliferation, migration, and invasion, and enhanced the apoptosis of UCEC cells. However, overexpression of MFAP2 abrogated the anti-tumor effect of TCF7L1 silencing on UCEC cell lines. Our study also revealed a negative correlation between MFAP2 and Immunoscore.

Conclusions: The present study suggested that MFAP2 could be involved in the carcinogenic progression of UCEC via the β-catenin/TCF7L1 axis. MFAP2 overexpression may contribute to immunosuppression in UCEC patients.

Introduction: Breast cancer (BC) remains a significant threat to women's health, necessitating the identification of new targets to inhibit its progression. Pyroptosis, a form of programmed cell death characterized by cellular swelling, distortion, and increased inflammatory factors, has emerged as a potential mechanism. High expression of exportin-T (XPOT) is linked to poor prognosis in BC patients, but its role in BC progression is not well understood.

Material and methods: We used the GEPIA database to analyze XPOT expression in BC and confirmed XPOT levels in BC tissues via immunohistochemistry. Western blotting was used to assess XPOT expression in various BC cell lines. We transfected small interfering RNAs (siRNAs) targeting XPOT and verified the transfection efficiency using Western blotting. The impact of si-XPOT on MCF-7 cell proliferation and apoptosis was measured using CCK-8 and TdT-mediated dUTP nick-end labeling assays. Scratch and Transwell assays were used to evaluate cell metastasis. Enzyme-linked immunosorbent assay was used to measure pyroptosis-associated inflammatory factors interleukin (IL)-1β and IL-18. Western blotting was used to detect pyroptosis-related proteins gasdermin D (GSDMD) and inflammasome components.

Results: XPOT expression was elevated in BC tissues, with higher levels in MCF-7 cells compared to other BC cells. Silencing XPOT reduced MCF-7 cell viability, migration, and invasion. Inhibition of XPOT increased pyroptosis-associated inflammatory factors, elevated N-terminal shear levels of GSDMD, and upregulated NLRP3, ASC, and cleaved-caspase1 expression. The pyroptosis inhibitor azalamellarin N reversed the effects induced by si-XPOT.

Conclusions: Silencing XPOT promotes pyroptosis in BC cells and inhibits BC progression, suggesting that targeting XPOT could offer new therapeutic avenues for BC treatment.

Introduction: Krüppel-like factor 7 (KLF7) exhibits pro-inflammatory properties in numerous diseases, but its precise function in acute lung injury (ALI) remains ambiguous. This study aimed to elucidate the molecular mechanism of KLF7 in type II alveolar epithelial cells under ALI conditions.

Material and methods: Cell Counting Kit-8 (CCK-8) assay and flow cytometry were employed to assess cell viability and apoptosis. The binding of KLF7 and LIM kinase 1 (LIMK1) promoter was tested by ChIP and dual-luciferase assays. GST pull-down and Co-IP assays verified the interaction between LIMK1 and serine arginine protein kinase 1 (SRPK1). Levels of inflammatory cytokines were measured by ELISA test. Western blot and quantitative real-time PCR were applied to assess the expression of related factors.

Results: KLF7 was upregulated in LPS-treated alveolar epithelial cells, and its knockdown attenuated cell apoptosis and inflammation by promoting cell viability and decreasing tumor necrosis factor α (TNF-α), interleukin 1 β (IL-1 β) and interleukin 6 (IL-6) levels. LIMK1 was transcriptionally activated by KLF7. The suppression of cell apoptosis and inflammation caused by KLF7 depletion was counteracted by LIMK1 overexpression. LIMK1 bound to SRPK1 protein to promote its phosphorylation. SRPK1 inhibition mitigated the effects of LIMK1 overexpression combined with KLF7 knockdown in LPS-treated alveolar epithelial cells.

Conclusions: KLF7 intensified the inflammatory response of alveolar epithelial cells under ALI conditions by modulating the LIMK1/SRPK1 axis.

Although generalized edema is a rare adverse event after drugs or vaccinations, here we report a case of generalized edema with systemic inflammatory reaction clinically similar to incomplete systemic capillary leak syndrome (SCLS), potentially triggered by COVID-19 immunization. The patient presented with generalized subcutaneous edema, a drop in blood pressure, elevated inflammatory biomarkers, and hypoalbuminemia after receiving the vaccine, with no other apparent cause than vaccination. Comprehensive diagnostic evaluation revealed no specific underlying cause. She was treated with glucocorticosteroids successfully. This case underscores the importance of recognizing rare but severe adverse events associated with vaccinations. Given the widespread administration of COVID-19 vaccines, it is crucial to identify and understand such reactions to ensure timely diagnosis and management. Therefore, we review the existing cases of SCLS following COVID-19 vaccination. Our review highlights the need for heightened vigilance and further research into the mechanisms underlying vaccine-induced phenomena to improve patient outcomes and vaccine safety profiles.

Introduction: Lung adenocarcinoma (LUAD), the most prevalent lung cancer type, poses a great threat to public health, with its incidence and mortality rates remaining alarmingly high. While ankyrin repeat domain-containing protein 22 (ANKRD22) is linked to the development of multiple cancers, the molecular mechanisms of its impact on the malignant progression of LUAD are not yet fully understood. This study seeks to elucidate the biological role of ANKRD22 in LUAD.

Material and methods: ANKRD22 expression in LUAD tissues and cells was assessed using the TCGA-LUAD database and quantitative reverse transcription polymerase chain reaction (qRT-PCR). The polarization of macrophages (derived from THP-1 cells) was examined through qRT-PCR, flow cytometry, and western blot to determine the influence of ANKRD22 on macrophage polarization. The effects of ANKRD22 knockdown on A549 cell proliferation and migration were measured using Cell Counting Kit-8 assay, colony formation, and Transwell assays. The impact of ANKRD22-induced macrophage M2 polarization on human umbilical vein endothelial cell (HUVEC) migration and angiogenesis was evaluated with Transwell and tube formation assays.

Results: The expression of ANKRD22 was elevated in LUAD tissue and cellular samples, and its overexpression promoted M2 polarization in macrophages. Blocking ANKRD22-mediated M2 polarization inhibited the migration and tube formation capacity of HUVEC cells.

Conclusions: Our findings showed that ANKRD22 mediates the malignant progression of LUAD by inducing M2 polarization of tumor-associated macrophages, thereby promoting angiogenesis.

Introduction: Sepsis-associated encephalopathy (SAE) is a complication posing a significant risk to patient health and survival. Microglial polarization and inflammation are key to the pathological progression of SAE. The p65 subunit is a component of the nuclear factor-κB (NF-κB) family. This study aimed to clarify the role of p65 in microglial polarization.

Material and methods: Human microglial HMC3 cells were treated with lipopolysaccharide (LPS). Cell viability was measured using a CCK-8 kit. Proinflammatory cytokine levels were evaluated using an ELISA assay. qRT-PCR or western blot assays were used to estimate mRNA or protein levels. The proportion of microglial M1 polarization was assessed using flow cytometry. The m6A-modified high mobility group box 1 (HMGB1) levels were analyzed using MeRIP-qPCR. Dual-luciferase reporter, chromatin immunoprecipitation (ChIP), and RNA immunoprecipitation (RIP) assays were conducted to validate the interactions between p65 and methyltransferase-like 3 (METTL3) or between METTL3 and HMGB1.

Results: LPS promoted microglial M1 polarization and enhanced p65, METTL3, and HMGB1 expression. Further, the inhibition of p65 ameliorated the LPS-induced M1 microglial polarization. p65 promotes HMGB1 m6A methylation by transcriptionally activating METTL3. Under LPS treatment, p65 enhances microglial M1 polarization via METTL3 activation. METTL3 aggravates LPS-induced microglial M1 polarization by positively regulating HMGB1 m6A modification.

Conclusions: p65 increases LPS-induced M1 polarization by promoting METTL3-mediated m6A modification of HMGB1 in HMC3 cells.

Introduction: Ulcerative colitis (UC) is a persistent inflammatory intestinal condition characterized by fluctuating disease activity (DA), with incompletely understood immunopathogenesis.

Material and methods: Our analysis included employing flow cytometry to examine CD8+ γδ T cells in the intestinal mucosa (IM) and the peripheral blood (PB) of UC patients as well as healthy controls. We focused on the presence of the HLA-DR activation indicator, the PD-1 immune suppression component, and the cytotoxic elements TRAIL, granzyme B, and perforin within CD8+ γδ T cells.

Results: A marked decline in the levels of IM CD8+ γδ T cells with increasing UC DA was observed. The immune status of these cells transitioned from activation in individuals with moderate UC activity to suppression in those experiencing severe UC activity. Correspondingly, cytotoxicity, indicated by granzyme B and perforin levels, was impaired in patients with severe UC activity. Notably, the proportions of IM CD8+ γδ T cells expressing granzyme B, PD-1, and HLA-DR were identified as potential biomarkers for distinguishing disease severity.

Conclusions: Our findings demonstrate the progression from immune activation to suppression and the concomitant impairment of cytotoxic activity in intestinal CD8+ γδ T cells as DA increases in UC, which may have implications for disease monitoring and therapeutic intervention.