JLE

European Cytokine Network

MENU

p38 MAPK inhibits JNK2 and mediates cytokine‐activated iNOS induction and apoptosis independently of NF‐κB translocation in insulin‐producing cells Volume 15, numéro 1, March 2004

Auteurs
Department of Medical Cell Biology, Uppsala University, Uppsala, Sweden.

The signaling pathways mediating nitric oxide production and apoptosis in pancreatic β‐cells are incompletely characterized. We report here that the inhibitor of p38 MAPK (p38), SB203580 (10‐100 µM) inhibits interleukin‐1β (IL‐1β)‐induced nitric oxide production in rat insulin‐producing RINm5F cells. SB203580 also counteracts apoptosis induced by a combination of IL‐1β and interferon‐γ. However, the contribution by p38 to the induction of inducible nitric oxide synthase (iNOS) and apoptosis is independent of NF‐κB nuclear translocation since SB203580 does not prevent IL‐1β‐induced DNA‐binding of this transcription factor. Furthermore, SB203580 alone leads to phosphorylation of JNK2 which may reflect inhibition of a p38‐activated phosphatase. It is concluded that p38 mediates cytokine‐induced iNOS‐induction and apoptosis independently of NF‐κB translocation. Moreover, a preventive effect on iNOS induction and apoptosis by inhibition of p38 may be partly masked due to simultaneous activation of JNK2 in pancreatic RINm5F cells.