Apigenin attenuated sepsis induced acute lung injury via polarizing macrophage towards M2 by blocking miR-146a →TLR7 interaction

IF 4.8 2区医学 Q2 IMMUNOLOGY International immunopharmacology Pub Date : 2025-03-14 DOI:10.1016/j.intimp.2025.114446

Jiafeng Geng , Zhihuan Zheng , Liangge Li , Zixuan Ren , Ge Tian , Jing Qin , Tong Zhao , Xiujing Feng

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Abstract

TLR7 (Toll-like receptor 7) has been indicated as an important sensor for single -stranded RNA contributes to systemic inflammation and mortality in acute lung injury (ALI), which is an acute diffuse inflammatory lung injury. Cumulative results show that macrophages contribute to the development and progression of ALI through the secretion of inflammatory cytokines/chemokines. Here we show that macrophage polarizes towards M1 phenotype and TLR7 signaling is activated in septic mice. Moreover, TLR7 deficiency promotes macrophage polarized towards M2 phenotype and attenuates ALI. Strikingly, the natural product of flavone apigenin (Xu et al., 2017 [1]) significantly improves sepsis-induced lung inflammation and lung injury via inhibiting inflammatory macrophages in a TLR7-dependent manner. Mechanically, Api blocked the binding of TLR7 with its agonist miR-146a. This finding reveals TLR7 is an important therapeutic target and Api as a modulator of TLR7 is a potential lead compound for treatment of septic diseases and inflammation related diseases.

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来源期刊

International immunopharmacology 医学-免疫学

CiteScore

8.40

自引率

3.60%

发文量

935

审稿时长

53 days

期刊介绍： International Immunopharmacology is the primary vehicle for the publication of original research papers pertinent to the overlapping areas of immunology, pharmacology, cytokine biology, immunotherapy, immunopathology and immunotoxicology. Review articles that encompass these subjects are also welcome. The subject material appropriate for submission includes: • Clinical studies employing immunotherapy of any type including the use of: bacterial and chemical agents; thymic hormones, interferon, lymphokines, etc., in transplantation and diseases such as cancer, immunodeficiency, chronic infection and allergic, inflammatory or autoimmune disorders. • Studies on the mechanisms of action of these agents for specific parameters of immune competence as well as the overall clinical state. • Pre-clinical animal studies and in vitro studies on mechanisms of action with immunopotentiators, immunomodulators, immunoadjuvants and other pharmacological agents active on cells participating in immune or allergic responses. • Pharmacological compounds, microbial products and toxicological agents that affect the lymphoid system, and their mechanisms of action. • Agents that activate genes or modify transcription and translation within the immune response. • Substances activated, generated, or released through immunologic or related pathways that are pharmacologically active. • Production, function and regulation of cytokines and their receptors. • Classical pharmacological studies on the effects of chemokines and bioactive factors released during immunological reactions.