Escherichia coli Maltose-Binding Protein Induces M1 Polarity of RAW264.7 Macrophage Cells via a TLR2- and TLR4-Dependent Manner.
Maltose-binding protein (MBP) is a critical player of the maltose/maltodextrin transport system in Escherichia coli. Our previous studies have revealed that MBP nonspecifically induces T helper type 1 (Th1) cell activation and activates peritoneal macrophages obtained from mouse. In the present study, we reported a direct stimulatory effect of MBP on RAW264.7 cells, a murine macrophage cell line. When stimulated with MBP, the production of nitric oxide (NO), IL-1β, IL-6 and IL-12p70, and the expressions of CD80, MHC class II and inducible nitric oxide synthase (iNOS) were all increased in RAW264.7 cells, indicating the activation and polarization of RAW264.7 cells into M1 macrophages induced by MBP. Further study showed that MBP stimulation upregulated the expression of TLR2 and TLR4 on RAW264.7 cells, which was accompanied by subsequent phosphorylation of IκB-α and p38 MAPK. Pretreatment with anti-TLR2 or anti-TLR4 antibodies largely inhibited the phosphorylation of IκB-α and p38 MAPK, and greatly reduced MBP-induced NO and IL-12p70 production, suggesting that the MBP-induced macrophage activation and polarization were mediated by TLR2 and TLR4 signaling pathways. The observed results were independent of lipopolysaccharide contamination. Our study provides a new insight into a mechanism by which MBP enhances immune responses and warrants the potential application of MBP as an immune adjuvant in immune therapies.
Department of Immunology, College of Basic Medical Science, Jilin University, 126 Xinmin Street, Changchun 130021, China. wangwan0106@yahoo.com.|Department of Breast Surgery, China-Japan Union Hospital, Jilin University, 126 Xiantai Blvd, Changchun 130033, China. wangwan0106@yahoo.com.
Wan
W
Wang
Department of Immunology, College of Basic Medical Science, Jilin University, 126 Xinmin Street, Changchun 130021, China. yuanhy@jlu.edu.cn.
Hong-Yan
HY
Yuan
Department of Immunology, College of Basic Medical Science, Jilin University, 126 Xinmin Street, Changchun 130021, China. liuguomu@126.com.
Guo-Mu
GM
Liu
Department of Immunology, College of Basic Medical Science, Jilin University, 126 Xinmin Street, Changchun 130021, China. niwh5566@jlu.edu.cn.
Wei-Hua
WH
Ni
Department of Immunology, College of Basic Medical Science, Jilin University, 126 Xinmin Street, Changchun 130021, China. fangfang5460@126.com.
Fang
F
Wang
Department of Immunology, College of Basic Medical Science, Jilin University, 126 Xinmin Street, Changchun 130021, China. taiguixiang@163.com.
Gui-Xiang
GX
Tai
D000818:Animals; D015415:Biomarkers / Q000378:metabolism; D016764:Cell Polarity / Q000187:drug effects*; D002470:Cell Survival / Q000187:drug effects; D016207:Cytokines / Q000378:metabolism; D029968:Escherichia coli Proteins / Q000494:pharmacology*; D015395:Histocompatibility Antigens Class I / Q000378:metabolism; D018836:Inflammation Mediators / Q000378:metabolism; D020935:MAP Kinase Signaling System / Q000187:drug effects; D008264:Macrophages / Q000166:cytology* / Q000187:drug effects / Q000201:enzymology / Q000378:metabolism*; D051379:Mice; D016328:NF-kappa B / Q000378:metabolism; D009569:Nitric Oxide / Q000378:metabolism; D052247:Nitric Oxide Synthase Type II / Q000378:metabolism; D033902:Periplasmic Binding Proteins / Q000494:pharmacology*; D010873:Pinocytosis / Q000187:drug effects; D000067996:RAW 264.7 Cells; D051195:Toll-Like Receptor 2 / Q000187:drug effects / Q000378:metabolism*; D051197:Toll-Like Receptor 4 / Q000187:drug effects / Q000378:metabolism*; D015854:Up-Regulation / Q000187:drug effects; D048051:p38 Mitogen-Activated Protein Kinases / Q000378:metabolism
D015415:Biomarkers; D016207:Cytokines; D029968:Escherichia coli Proteins; D015395:Histocompatibility Antigens Class I; D018836:Inflammation Mediators; C461619:MalE protein, E coli; D016328:NF-kappa B; D033902:Periplasmic Binding Proteins; D051195:Toll-Like Receptor 2; D051197:Toll-Like Receptor 4; D009569:Nitric Oxide; D052247:Nitric Oxide Synthase Type II; D048051:p38 Mitogen-Activated Protein Kinases