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

IF 4.7 2区医学 Q2 IMMUNOLOGY International immunopharmacology Pub Date : 2025-04-16 Epub 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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芹菜素通过阻断miR-146a→TLR7相互作用，使巨噬细胞向M2极化，减轻脓毒症诱导的急性肺损伤

TLR7 （toll样受体7）是单链RNA在急性肺损伤（ALI）中参与全身性炎症和死亡的重要传感器，是一种急性弥漫性肺损伤。累积结果表明，巨噬细胞通过分泌炎性细胞因子/趋化因子参与ALI的发生和进展。我们发现巨噬细胞向M1表型极化，TLR7信号在脓毒症小鼠中被激活。此外，TLR7缺失促进巨噬细胞向M2表型极化，并减弱ALI。引人注目的是，天然产物黄酮类芹菜素（Xu et al., 2017[1]）通过tlr7依赖的方式抑制炎性巨噬细胞，显著改善败血症诱导的肺部炎症和肺损伤。机械上，Api阻断了TLR7与其激动剂miR-146a的结合。这一发现表明TLR7是一个重要的治疗靶点，Api作为TLR7的调节剂是治疗感染性疾病和炎症相关疾病的潜在先导化合物。

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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.