ROLES OF PROTEIN PHOSPHATASE 2A IN IL-6 SIGNAL-TRANSDUCTION IN HEP3B CELLS

IL-6 is a pleiotropic cytokine that modulates the diverse functions of hepatocytes such as acute phase responses and inflammation. When huma n hepatoma cells, Hep3B cells, were treated with IL-6, p140 was phosph orylated rapidly and reached its maximal rate at 1 min after treatment . Okadaic acid, an inhibitor of protein phosphatase 1 and 2A, affected IL-6-induced p140 phosphorylation. Interferon regulatory factor-1 (IR F-1) is a transcription factor on the enhancer of type I interferons, and its gene expression is induced by IL-6. When IRF-1 promoter-lucife rase construct was transfected into Hep3B cells, okadaic acid increase d IL-6-induced IRF-1 promoter activity. In addition, co-transfection o f protein phosphatase 2A (PP2A) antisense constructs further increased IL-6-induced IRF-1 promoter activity, suggesting that PP2A is involve d in IL-6 signaling. In addition, IL-6 directly induced the PP2A phosp horylation. PP2A phosphorylation was maximal at 1 min after IL-6 stimu lation, but it was not induced by other inflammatory cytokines such as TNF-alpha or TGF-beta. Furthermore, IL-6 activated PP2A activity simu ltaneously. Taken together, these data indicate that IL-6 modulates th e functions of PP2A which is involved in downstream events of IL-6 sig naling in Hep3B. (C) 1998 Elsevier Science B.V. All rights reserved.