跨膜 TNF-α 反向信号通过调节 MCPIP1/SIRT1/NF-κB 通路缓解脂多糖诱发的炎症

IF 1.1 4区 医学 Q4 IMMUNOLOGY
Chenxi Li, Mingxin Lin, Xiujuan Li, Lijin Chen, Yubin Lin, Huiming Ye
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引用次数: 0

摘要

本文章由计算机程序翻译,如有差异,请以英文原文为准。
Transmembrane TNF-α Reverse Signaling Alleviates Lipopolysaccharide-induced ‎Inflammation by Regulating the MCPIP1/SIRT1/NF-κB Pathway.

Background: Studies have demonstrated that transmembrane tumor necrosis factor-α (tmTNF-α) plays an anti-inflammatory role. tmTNF-α has a dual function, acting as both a signaling ligand and a receptor that transmits reverse signaling to cells expressing tmTNF-α. However, the role and mechanisms of tmTNF-α reverse signaling in sepsis are not fully understood.

Objective‎: To explore the potential role and mechanisms of tmTNF-α reverse signaling in lipopolysaccharide (LPS)-induced inflammation.

Methods‎: The expression levels of tmTNF-α and TNF-α mRNA were evaluated using flow cytometry and real-time PCR, respectively. We employed the anti-TNF-α drug infliximab to stimulate tmTNF-α reverse signaling and measured interleukin-6 (IL-6) and monocyte chemoattractant protein (MCP)-1 production through real-time PCR and ELISA in THP-1-derived macrophages. The location of p65 was determined through immunofluorescence assay. The phosphorylation and acetylation of p65, as well as the expression levels of MCP-induced protein 1 (MCPIP1) and Sirtuin 1 (SIRT1), were evaluated using western blotting.

Results: Our findings revealed that tmTNF-α reverse signaling reduced the expression of IL-6 and MCP-1 triggered by LPS. tmTNF-α reverse signaling inhibited the nuclear translocation of p65, suppressed p65 phosphorylation and acetylation, and upregulated the expression of negative regulatory molecules MCPIP1 and SIRT1 in the LPS/ toll-like receptor 4 (TLR4) signaling pathway.

Conclusion‎: This study demonstrates that tmTNF-α reverse signaling plays a negative regulatory role in inflammation triggered by LPS by inhibiting the TLR4/ nuclear factor kappa B (NF-κB) signaling pathway. This study helps to further understand the function of tmTNF-α reverse signaling and offers new therapeutic possibilities for sepsis and other inflammatory disease conditions.

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来源期刊
Iranian Journal of Immunology
Iranian Journal of Immunology Medicine-Immunology and Allergy
CiteScore
1.60
自引率
0.00%
发文量
50
审稿时长
12 weeks
期刊介绍: The Iranian Journal of Immunology (I.J.I) is an internationally disseminated peer-reviewed publication and publishes a broad range of experimental and theoretical studies concerned with all aspects of immunology.
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