LTA and LPS mediated activation of protein kinases in the regulation of inflammatory cytokines expression in macrophages.

BACKGROUND Lipoteichoic acid (LTA) and lipopolysaccharide (LPS), the toxicants from bacteria, are potent inducers of inflammatory cytokines, such as tumor necrosis factor-alpha (TNF) and interleukin-1beta (IL-1). Although LTA is much less reported than that on LPS, LTA is regarded as the gram-positive equivalent to LPS in some aspects. We investigated the LTA-induced signal transduction and biological effects, as well as to compare the effect of LTA with that of LPS. METHODS Kinase assay, ELISA and RT-PCR were performed to delineate LTA and LPS signaling as well as to determine the secretion and RNA expression of TNF and IL-1. RESULTS Src, Lyn and MAPKs are involved in LTA and LPS signaling in murine macrophages. Additionally, blockades of PKC, PI3K and p38, respectively, caused significant inhibition of both LTA- and LPS-induced proIL-1/IL-1 and TNF expression. ERK inactivation moderately reduced LTA- and LPS-induced proIL-1/IL-1, but considerably reduced TNF expression. Inhibition of JNK engendered super-induction of IL-1 secretion, but diminished TNF secretion. Strikingly, both IL-1 and TNF protein induction were declined by overexpression of dominant negative form of JNK. CONCLUSIONS The results clarify the similarity and difference between LTA- and LPS-mediated signal transduction and induction of inflammatory cytokines in macrophages.