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

Inn Oc Han; Ki-Wan Kim; Jong Hoon Ryu; Won-Ki Kim

doi:10.1016/s0304-3940(02)00218-5

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

Neurosci Lett. 2002 May 31;325(1):9-12. doi: 10.1016/s0304-3940(02)00218-5.

Authors

Inn Oc Han¹, Ki-Wan Kim, Jong Hoon Ryu, Won-Ki Kim

Affiliation

¹ Department of Pharmacology, College of Medicine, Ewha Institute of Neuroscience, Ewha Women's University, 70 Chongro-6-ga, Chongro-ku, Seoul 110-783, South Korea.

PMID: 12023055
DOI: 10.1016/s0304-3940(02)00218-5

Abstract

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.

MeSH terms

Animals
Cell Line
Enzyme Inhibitors / pharmacology
Flavonoids / pharmacology
Imidazoles / pharmacology
Interferon-gamma / pharmacology
JNK Mitogen-Activated Protein Kinases
Lipopolysaccharides / pharmacology*
Mice
Microglia / drug effects*
Microglia / enzymology*
Mitogen-Activated Protein Kinases / antagonists & inhibitors
Mitogen-Activated Protein Kinases / metabolism
Mitogen-Activated Protein Kinases / physiology*
Nitric Oxide / biosynthesis
Nitric Oxide Synthase / antagonists & inhibitors
Nitric Oxide Synthase / genetics
Nitric Oxide Synthase / metabolism*
Nitric Oxide Synthase Type II
Pyridines / pharmacology
RNA, Messenger / metabolism
Time Factors
p38 Mitogen-Activated Protein Kinases

Substances

Enzyme Inhibitors
Flavonoids
Imidazoles
Lipopolysaccharides
Pyridines
RNA, Messenger
Nitric Oxide
Interferon-gamma
Nitric Oxide Synthase
Nitric Oxide Synthase Type II
Nos2 protein, mouse
JNK Mitogen-Activated Protein Kinases
Mitogen-Activated Protein Kinases
p38 Mitogen-Activated Protein Kinases
SB 203580
2-(2-amino-3-methoxyphenyl)-4H-1-benzopyran-4-one