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Bronchoalveolar Lavage Exosomes in Lipopolysaccharide-induced Septic Lung Injury
Published on: May 21, 2018
Apigenin attenuated sepsis induced acute lung injury via polarizing macrophage towards M2 by blocking miR-146a →TLR7
Jiafeng Geng1, Zhihuan Zheng1, Liangge Li1
1Shandong Province University Clinical Immunology Translational Medicine Laboratory, The First Affiliated Hospital of Shandong First Medical University & Shandong Provincial Qianfoshan Hospital, Jingshi Road 16766, Jinan, Shandong 250014, China; School of Clinical and Basic Medical Sciences, Shandong First Medical University& Shandong Academy of Medical Sciences, Jinan 250117, Shandong, China.
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.
Insights
Toll-like receptor 7 (TLR7) signaling drives acute lung injury (ALI) by activating inflammatory macrophages. The natural compound apigenin inhibits TLR7, reducing lung inflammation and injury in sepsis models.
Area of Science:
- Immunology
- Molecular Biology
- Pharmacology
Background:
- Toll-like receptor 7 (TLR7) senses single-stranded RNA, contributing to systemic inflammation and acute lung injury (ALI).
- Macrophages play a critical role in ALI pathogenesis through inflammatory cytokine and chemokine secretion.
- TLR7 signaling and M1 macrophage polarization are activated in septic mice, exacerbating ALI.
Purpose of the Study:
- To investigate the role of TLR7 signaling in macrophage polarization and ALI development during sepsis.
- To evaluate the therapeutic potential of apigenin (Api) in mitigating sepsis-induced lung inflammation and injury.
Main Methods:
- Analysis of macrophage polarization (M1/M2 phenotypes) in septic mice with and without TLR7.
- Assessment of ALI severity in TLR7-deficient mice.
- Administration of apigenin to septic mice and evaluation of its effects on lung inflammation and injury.
- Investigation of the molecular mechanism of apigenin's action, specifically its interaction with TLR7 and miR-146a.
Main Results:
- TLR7 deficiency promoted a shift towards M2 macrophage polarization and attenuated ALI.
- Apigenin significantly reduced sepsis-induced lung inflammation and injury by inhibiting inflammatory macrophages.
- Apigenin was found to block the interaction between TLR7 and its agonist, miR-146a.
Conclusions:
- TLR7 signaling is a key driver of M1 macrophage polarization and ALI in sepsis.
- Apigenin demonstrates therapeutic potential for treating sepsis-induced lung inflammation and injury by modulating TLR7 activity.
- Targeting TLR7 with compounds like apigenin offers a promising strategy for inflammatory and septic diseases.
