TY  - EJOU
AU  - Saldeen, Johan 
AU  - Welsh, Nils 

TI  - p38 MAPK inhibits JNK2 and mediates cytokine-activated iNOS induction and apoptosis independently of NF-κB translocation in insulin-producing cells
T2  - European Cytokine Network

PY  - 2004
VL  - 15
IS  - 1
SN  - 1952-4005

AB  - 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. Further-more,
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.
KW  - β-cell
KW  -  SB203580
KW  -  JNK
KW  -  nitric oxide
KW  -  interleukin-1β
KW  -  interferon-γ

DO  -