Journal of Inflammation Research (Aug 2022)
Alpha-Momorcharin Inhibits Proinflammatory Cytokine Expression by M1 Macrophages but Not Anti-Inflammatory Cytokine Expression by M2 Macrophages
Abstract
Kejun Peng,1,* Nianhua Deng,1,* Yao Meng,1,* Qianchuan He,2 Hao Meng,3 Ting Luo,4 Yanru Wei,1 Yue Kang,1 Xiaodong Zhou,1 Fubing Shen1 1School of Laboratory Medicine, Chengdu Medical College, Chengdu, People’s Republic of China; 2Public Health Sciences Division, Fred Hutchinson Cancer Research Center, Seattle, WA, 98109, USA; 3PKU-IDG/McGovern Institute for Brain Research, Peking-Tsinghua Center for Life Sciences, Peking University School of Life Sciences, Beijing, People’s Republic of China; 4Wuhan Corebiolab Co., Ltd, Wuhan, People’s Republic of China*These authors contributed equally to this workCorrespondence: Fubing Shen, School of Laboratory Medicine, Chengdu Medical College, No. 783 Xindu Avenue, Xindu District, Chengdu, 610500, People’s Republic of China, Tel +86 28 62739522, Email [email protected]: Alpha-momorcharin (α-MMC) is a natural medicine derived from bitter melon and has been found to exert immunomodulatory effects. Our previous study indicated that α-MMC can regulate cytokine release from monocytes, but it remains unknown about its regulatory effect on different types of cytokines, such as inflammatory cytokines or anti-inflammatory cytokines.Methods: LPS-induced M1-type macrophages model and IL-4-induced M2-type macrophages model were established, and the expression of proinflammatory cytokines and anti-inflammatory cytokines were assessed by ELISA after α-MMC was administered. Then, a LPS-induced acute pneumonia mouse model was established, the proinflammatory cytokines levels and inflammatory lesions in lung tissues were examined by ELISA or H&E staining. Furthermore, omics screening analysis and Western blotting verification were performed on TLR4 and JAK1-STAT6 signalling pathway-related proteins to elucidate the regulatory mechanism of α-MMC in those M1 macrophages and M2 macrophages.Results: At a noncytotoxic dose of 0.3 μg/mL, α-MMC significantly inhibited the LPS-induced expression of inflammatory cytokines, such as TNF-α, IL-1β, IL-6, IL-8, MIP-1α and MCP-1, by M1 macrophages in a time-dependent manner, but α-MMC did not inhibit the IL-4-induced synthesis of anti-inflammatory cytokines, such as IL-10, IL-1RA, EGF, VEGF, TGF-β and CCL22, by M2 macrophages. Moreover, α-MMC also inhibited inflammatory cytokine expression in an LPS-induced acute pneumonia mouse model and alleviated inflammation in lung tissues. Furthermore, omics screening and Western blotting analysis confirmed that α-MMC inhibited TAK1/p-TAK1 and subsequently blocked the downstream MAPK and NF-κB pathways, thus inhibiting the LPS-induced inflammatory cytokine expression.Conclusion: Our results reveal that α-MMC inhibits proinflammatory cytokine expression by M1 macrophages but not anti-inflammatory cytokine expression by M2 macrophages. The efficacy of α-MMC in selectively inhibiting proinflammatory cytokine expression renders it particularly suitable for the treatment of severe inflammation and autoimmune diseases characterized by cytokine storms.Keywords: α-MMC, M1 macrophage, proinflammatory cytokine, TLR4-NF-κB/MAPK
