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

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.