Open AccessSophora flavescens protects against mycobacterial Trehalose Dimycolate-induced lung granuloma by inhibiting inflammation and infiltration of macrophages
Author(s) -
Dehua Liu,
Barbara Pui Chan,
Ling Cheng,
Miranda SinMan Tsang,
Jianhua Zhu,
Chung Wong,
Delong Jiao,
Helen Yau-Tsz Chan,
Ping Chung Leung,
Christopher WaiKei Lam,
Chun Kwok Wong
Publication year - 2018
Publication title -
scientific reports
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.24
H-Index - 213
ISSN - 2045-2322
DOI - 10.1038/s41598-018-22286-w
Subject(s) - inflammation , sophora flavescens , microbiology and biotechnology , immune system , mycobacterium tuberculosis , immunology , granuloma , chemokine , biology , medicine , tuberculosis , pathology , matrine , neuroscience
The immune system responds to Mycobacterium tuberculosis (MTB) infection by forming granulomas to quarantine the bacteria from spreading. Granuloma-mediated inflammation is a cause of lung destruction and disease transmission. Sophora flavescens (SF) has been demonstrated to exhibit bactericidal activities against MTB. However, its immune modulatory activities on MTB-mediated granulomatous inflammation have not been reported. In the present study, we found that flavonoids from Sophora flavescens (FSF) significantly suppressed the pro-inflammatory mediators released from mouse lung alveolar macrophages (MH-S) upon stimulation by trehalose dimycolate (TDM), the most abundant lipoglycan on MTB surface. Moreover, FSF reduced adhesion molecule (LFA-1) expression on MH-S cells after TDM stimulation. Furthermore, FSF treatment on TDM-activated lung epithelial (MLE-12) cells significantly downregulated macrophage chemoattractant protein (MCP-1/CCL2) expression, which in turn reduced the in vitro migration of MH-S to MLE-12 cells. In addition, FSF increased the clearance of mycobacterium bacteria ( Mycobacterium aurum ) in macrophages. FSF mainly affected the Mincle-Syk-Erk signaling pathway in TDM-activated MH-S cells. In TDM-induced mouse granulomas model, oral administration with FSF significantly suppressed lung granulomas formation and inflammation. These findings collectively implicated an anti-inflammatory role of FSF on MTB-mediated granulomatous inflammation, thereby providing evidence of FSF as an efficacious adjunct treatment during mycobacterial infection.