Effects of mitogen-activated protein kinase inhibitors or phosphodiesterase inhibitors on interleukin-1-induced cytokines production in synovium-derived cells

The effects of mitogen-activated protein (MAP) kinase inhibitors or phospho diesterase (PDE) inhibitors on interleukin (IL)-1-induced cytokines product ion in synovium-derived cells were investigated. Human synoviocyte (HS) or synovial sarcoma (SW982) stimulated by IL-1 beta (100 ng/ml) produced vario us cytokines including IL-6, IL-8, GRO alpha, VEGF, basic FGF and tumor nec rosis factor alpha (TNF alpha) in vitro. SB202190 or SB203580, an inhibitor of p38 MAP kinase, inhibited all cytokines production in both cells. PD980 59, an inhibitor of MAP kinase kinase (MEK), inhibited IL-6, IL-8 and basic FGF production in HS and all cytokines production except basic FGF in SW98 2. However, many of its effects were weaker than those of SB202190 or SB203 580. Quazinone, an inhibitor of cyclic GMP-inhibited PDE, scarcely affected cytokines production in both cells. Rolipram or RO201724, an inhibitor of cyclic AMP-specific PDE, inhibited IL-8 and basic FGF production in HS and TNF alpha production in SW982, however, it enhanced the other cytokines pro duction in SW982. These results suggest that the activation of MAP kinase c ascade may be important for IL-l-induced cytokines production in synovium-d erived cells. On the other hand, the role of cyclic AMP may be dependent on cell and cytokine types. (C) 1999 Elsevier Science B.V. All rights reserve d.