Prostaglandin E1 inhibits interleukin-6-induced MCP-1 expression by interfering specifically in IL-6-dependent ERK1/2- but not STAT3 activation
Résumé
Interleukin-6 exerts pro- as well as anti-inflammatory activities. Beside many other activities, IL-6 is the major inducer of acute phase proteins in the liver, acts a differentiation factor for blood cells, as migration factor for T-cells and is a potent inducer of the chemokine monocyte chemoattractant protein-1 (MCP-1). Recent studies focussed on the negative regulation of interleukin 6 signal transduction through the IL-6-induced feedback inhibitors SOCS1 and SOCS3 or the protein tyrosine phosphatases SHP2 and TcPTP. Studies on the cross-talk between pro-inflammatory mediators (interleukin-1, tumour necrosis factor, lipopolysaccharide) and interleukin-6 elucidated further regulatory mechanisms. Less is known about the regulation of IL-6 signal transduction by hormones/cytokines signalling through G-protein-coupled receptors. This is particularly surprisingly since many of these hormones (such as prostaglandins and chemokines) play an important role in inflammatory processes. Here, we investigated the inhibitory activity of prostaglandin E1 on IL-6-induced MCP-1 expression and elucidated the underlying molecular mechanism. Surprisingly, PGE1 does not affect IL-6-induced STAT3- but ERK1/2-activation which is crucial of IL-6-dependent expression of MCP-1. In summary, a specific cross-talk between the adenylate cyclase cascade and the IL-6-induced MAPK cascade and its impact on IL-6-dependent gene expression was discovered.
Origine : Fichiers produits par l'(les) auteur(s)
Loading...