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Int. J. Mol. Sci. 2015, 16(5), 9896-9909; doi:10.3390/ijms16059896

Escherichia coli Maltose-Binding Protein Induces M1 Polarity of RAW264.7 Macrophage Cells via a TLR2- and TLR4-Dependent Manner

1
Department of Immunology, College of Basic Medical Science, Jilin University, 126 Xinmin Street, Changchun 130021, China
2
Department of Breast Surgery, China-Japan Union Hospital, Jilin University, 126 Xiantai Blvd, Changchun 130033, China
*
Author to whom correspondence should be addressed.
Academic Editor: Kamal D. Moudgil
Received: 7 March 2015 / Revised: 23 April 2015 / Accepted: 24 April 2015 / Published: 30 April 2015
(This article belongs to the Special Issue Mechanism of Action and Applications of Cytokines in Immunotherapy)
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Abstract

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. View Full-Text
Keywords: maltose-binding protein; classically activated macrophages; toll-like receptor 2; toll-like receptor 4 maltose-binding protein; classically activated macrophages; toll-like receptor 2; toll-like receptor 4
This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. (CC BY 4.0).

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MDPI and ACS Style

Wang, W.; Yuan, H.-Y.; Liu, G.-M.; Ni, W.-H.; Wang, F.; Tai, G.-X. Escherichia coli Maltose-Binding Protein Induces M1 Polarity of RAW264.7 Macrophage Cells via a TLR2- and TLR4-Dependent Manner. Int. J. Mol. Sci. 2015, 16, 9896-9909.

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