p38 mitogen-activated protein kinase mediates lipopolysaccharide, not interferon-gamma, -induced inducible nitric oxide synthase expression in mouse BV2 microglial cells.

The present study examined the role of mitogen - activated protein kinases (MAPKs) in inducible nitric oxide synthase (iNOS) induction by lipopolysaccharide (LPS) or interferon - gamma (IFN - gamma) in the murine microglial cell line BV2 cells. LPS rapidly (<2 h) induced iNOS mRNA expression whereas IFN - gamma did not within 8 h after stimulation. LPS activated three MAPK subtypes, extracellular signal - regulated kinase (ERK), p38 and c - Jun N - terminal kinase (JNK) as early as 15 min after stimulation. In contrast, IFN - gamma activated only ERK after 6 h of stimulation and did not alter the activity of p38 and JNK. LPS-induced iNOS expression was markedly decreased by the p38 inhibitor SB203580, but not by the MAPK or ERK kinase inhibitor PD98059. IFN - gamma - induced nitric oxide (NO) generation was partially inhibited by PD98059 and SB203580 only in combination. The results demonstrate that MAPKs differentially mediate NO production by LPS - and IFN - gamma in BV2 cells.