OKADAIC ACID, AN INHIBITOR OF PROTEIN PHOSPHATASE-1 AND PHOSPHATASE-2A, INHIBITS INDUCTION OF ACUTE-PHASE PROTEINS BY INTERLEUKIN-6 ALONE OR IN COMBINATION WITH INTERLEUKIN-1 IN HUMAN HEPATOMA-CELL LINES

Okadaic acid (OA), a specific inhibitor of protein phosphatases 1 and 2A, inhibited in a dose-dependent manner (5-20 nM) the induction of C-reactive protein (CRP), serum amyloid A (SAA) and fibrinogen by interleukin-6 (IL-6) plus interleukin-1 (IL-1), and of fibrinogen by IL-6 alone, in Hep 3B cells. Induction of alpha-1-proteinase inhibitor (alpha-1-PI) by IL-6 plus IL-I or IL-6 alone was not significantly affected by OA up to concentrations of 20 nm, above which concentration OA was toxic in Hep 3B cells. OA also inhibited the induction of CRP, fibrinogen and alpha-1-PI by IL-6 in the NPLC/PRF/5 cell line, albeit at a higher concentration (80 nm). These results suggest that the signal transduction mechanisms regulating induction of acute-phase proteins by IL-6, either alone or in combination with IL- 1, are mediated by activation of protein phosphatases 1 and/or 2A.