TGR5 Reduces Lipopolysaccharide-Induced Macrophage Inflammatory Response through Regulating the STAT3 Signaling Pathway

作者全名："Yu, Chao; Liu, Yin; Shi, Yuan"

作者地址："[Yu, Chao; Liu, Yin; Shi, Yuan] Chongqing Med Univ, Dept Neonatol, Childrens Hosp, Chongqing 400014, Peoples R China; [Yu, Chao; Liu, Yin; Shi, Yuan] Chongqing Med Univ, Chongqing Key Lab Pediat, Childrens Hosp, Chongqing 400014, Peoples R China; [Yu, Chao; Liu, Yin; Shi, Yuan] China Int Sci & Technol Cooperat Base Child Dev &, Key Lab Child Dev & Disorders, Natl Clin Res Ctr Child Hlth & Disorders, Minist Educ, Chongqing 400014, Peoples R China"

通信作者："Shi, Y (通讯作者)，Chongqing Med Univ, Dept Neonatol, Childrens Hosp, Chongqing 400014, Peoples R China.; Shi, Y (通讯作者)，Chongqing Med Univ, Chongqing Key Lab Pediat, Childrens Hosp, Chongqing 400014, Peoples R China.; Shi, Y (通讯作者)，China Int Sci & Technol Cooperat Base Child Dev &, Key Lab Child Dev & Disorders, Natl Clin Res Ctr Child Hlth & Disorders, Minist Educ, Chongqing 400014, Peoples R China."

来源：JOURNAL OF BIOLOGICAL REGULATORS AND HOMEOSTATIC AGENTS

ESI学科分类：BIOLOGY & BIOCHEMISTRY

WOS号：WOS:001148114000001

JCR分区：Q4

影响因子：0.8

年份：2024

卷号：38

期号：1

开始页：811

结束页：822

文献类型：Article

关键词：TGR5; STAT3; acute lung injury; alveolar macrophage

摘要："Background: The immune response mediated by alveolar macrophages is critical in lung injury pathogenesis. Takeda G proteincoupled receptor 5 (TGR5) is implicated in the immune cell-mediated responses. This study explored the effects and underlying mechanisms of TGR5 in the lipopolysaccharide (LPS)-induced inflammatory responses in alveolar macrophages. Methods: Mouse alveolar macrophage (MH-S) cells were exposed to LPS, and TGR5 knockdown cells were established using the Clustered Regularly Interspaced Short Palindromic Repeats/Cas9 (CRISPR/Cas9) method. The changes of inflammation responses and macrophage polarity after TGR5 knockdown in LPS-treated MH-S cells were analyzed by quantitative reverse transcriptase real-time polymerase chain reaction (qRT-PCR) and enzyme-linked immunosorbent assay (ELISA). The impact of TGR5 knockdown on protein expression related to the signal transducer and activator of the transcription 3 (STAT3) pathway was assessed through Western blot. Finally, MH-S cells were treated with chenodeoxycholic acid (CDCA, a TGR5 agonist) or cucurbitacin B (CuB, a STAT3 inhibitor), and changed in the expression of STAT3 pathway proteins and the macrophage activation markers inducible nitric oxide synthase (iNOS) and cluster of differentiation 206 (CD206) were detected using Western blot and qRT-PCR. Results: LPS stimulation enhanced inflammation responses in MH-S cells, with TGR5 knockdown exacerbating LPS-induced inflammation. Additionally, TGR5 knockdown promoted LPS-induced M1 polarization of macrophages, increasing Interleukin (IL)-6 expression and the phospho (p)-STAT3/STAT3 ratio in LPS-induced MH-S cells. Treatment with CDCA or CuB reduced IL-6 expression and the p-STAT3/STAT3 ratio, inhibiting M1 polarization of macrophages in TGR5 knockdown MH-S cells. Conclusions: TGR5 inhibits inflammation and promotes macrophage polarization toward the M2 phenotype in LPS-induced MH-S cells. Its effect is achieved, in part, by inhibiting the STAT3 signaling pathway."

基金机构：National Key Research and Development Program of China [2022YFC2704802]

基金资助正文：Funding This work was supported by the National Key Research and Development Program of China (2022YFC2704802) .