Involvement of Syk protein tyrosine kinase in LPS-induced responses in macrophages

Abstract

Syk kinase is best known as a critical component of immunoreceptor signaling in leukocytes. Activation of Syk following cross-linking of Fcgamma and Fcepsilon receptors on macrophages, mast cells, and other cells induces various inflammatory events. We hypothesized that Syk is involved in inflammatory responses induced by the lipopolysaccharide (LPS). We studied the role of Syk using its inhibition by antisense oligonucleotides, or small interfering RNA. Our data demonstrated that in vivo inhibition of Syk caused down-regulation of LPS-induced responses in rat alveolar macrophages. In in vitro experiments, inhibition of Syk in rat peritoneal macrophages, as well as in human myelomonocyte cell line THP-1 also caused a decrease in LPS-induced cytokine release. Our data support the hypothesis that, in macrophages, Syk is involved in LPS-induced intracellular signaling pathways leading to the release of pro-inflammatory mediators. Understanding the role of Syk in LPS-induced signaling may help in developing new therapeutic tools for inflammatory disorders.

Inhibition of spleen tyrosine kinase as treatment of postoperative ileus

“…Indeed, inhibition of Syk signalling in rat alveolar and in peritoneal macrophages and in the monocytic cell line THP-1 resulted in reduction of pro-inflammatory cytokine secretion 14. In the present study, we evaluated the effect of GSK143 on cultured macrophages treated with endotoxin.…”

Tyrosine Kinases and Inflammatory Signalling

“…Syk has been shown to be phosphorylated in response to TLR4 (LPS) and TLR9 (CpG) stimulation in a range of cell types (including murine macrophages [112,113], human monocytic cell lines [114], neutrophils [115,116] and fibroblasts [117]). How this phosphorylation is achieved is unclear, although in neutrophils and THP-1 monocytic cells Syk has been shown to be physically associated with both TLR9, TLR4 and MyD88, [114,116], despite the lack of ITAMs in these molecules Fig.…”

Suppressive effects of methoxyflavonoids isolated from Kaempferia parviflora on inducible nitric oxide synthase (iNOS) expression in RAW 264.7 cells

“…SYK also induces the activation of NF-B which regulates the transcription of genes encoding pro-inflammatory molecules (Takada and Aggarwal, 2004). Evidence of the involvement of SYK in the production of NO is still lacking, but SYK is involved in the regulation of LPS-induced signaling in macrophages (Ulanova et al, 2007). Recently, several flavonoids (e.g.…”