MerTK Downregulates Lipopolysaccharide-Induced Inflammation Through SOCS1 Protein but Does Not Affect Phagocytosis of Escherichia coli in Macrophages.

Abstract

Bacterial lipopolysaccharide (LPS) induces inflammatory response via toll-like receptor 4 (TLR4). However, this response must be strictly regulated because unbalanced overproduction of pro-inflammatory cytokines can lead to tissue damage and even be fatal. Herein, we explore whether Mer receptor tyrosine kinase (MerTK) regulates Escherichia coli (E. coli) LPS-induced inflammation and mediates phagocytosis of E. coli by macrophages. The results showed that LPS activated TLR4 signaling pathway and induced MerTK pathway in RAW264.7 macrophages, including suppressor of cytokine signaling1 (SOCS1). Preincubation with MerTK-specific blocking antibody (MerTK-Ab) markedly suppressed LPS-induced expression of phosphorylated MerTK, while further promoted LPS-induced production of TNF-α, IL-6, and IL-1β as well as phosphorylation of IκB-α and p65. Likewise, MerTK-Ab prevented LPS-induced SOCS1 expression. Furthermore, LPS-induced production of pro-inflammatory cytokines and activation of NF-κB were increased by transfection with SOCS1 siRNA. Additionally, we demonstrated that MerTK was dispensable in phagocytosis of E. coli by RAW264.7 or peritoneal macrophages. Collectively, these results indicate that MerTK downregulates LPS-induced inflammation through SOCS1 protein without affecting phagocytosis of E. coli in macrophages.