The present study examined the role of mitogen-activated protein kinases (MAPKs) in inducible nitric oxide synthase (iNOS) induction by lipopolysaccharide (LPS) or interferon-γ (IFN-γ) in the murine microglial cell line BV2 cells. LPS rapidly (<2 h) induced iNOS mRNA expression whereas IFN-γ 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-γ 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-γ-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-γ in BV2 cells.
- Extracellular signal-regulated kinase
- Inducible nitric oxide synthase
- Nitric oxide
- c-Jun N-terminal kinase
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