Journal
IMMUNOLOGIC RESEARCH
Volume 67, Issue 1, Pages 77-83Publisher
HUMANA PRESS INC
DOI: 10.1007/s12026-018-9039-y
Keywords
LPS; TLR4; FcR; ERK
Categories
Funding
- National Science Foundation of China [91529304, 81473230, 81673468]
- Natural Science Foundation of Jiangsu Province [BK20170732]
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Fc receptor common signaling chain (FcR), a common subunit shared by Fc receptors (FcRI, III, IV, FcRI, and Fc epsilon RI), is an important immune regulator both in innate and adaptive immunity. Previous studies have shown that FcR was a potential target of inflammatory diseases, whereas the role of FcR in sepsis has been poorly understood. In this study, we found that deficiency of FcR resulted in increased survival in lipopolysaccharide (LPS)/D-galactosamine and E. coli-induced sepsis in mice. This protective effect was characterized by decreased TNF-, IL-6, and IL-10. Further experiments in bone marrow-derived macrophages (BMDMs) in vitro also showed that FcR deficiency resulted in decreased production of TNF-, IL-6, and IL-10 upon LPS stimulation. The mechanism study showed that FcR was physiologically associated with toll-like receptor 4 (TLR4), and tyrosine phosphorylation of FcR mediated TLR4 signaling pathway, followed by increased ERK phosphorylation upon LPS stimulation. Our results suggest that FcR might be a potential therapeutic target of sepsis.
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