p38 MAPK and NF-kappaB are required for LPS-induced RANTES production in immortalized murine microglia (BV-2).
- Author:
Sae Byeol JANG
1
;
Kweon Haeng LEE
Author Information
1. Department of Pharmacology, College of Medicine, Catholic University of Korea, Seoul, South Korea. lkh@cmc.cuk.ac.kr
- Publication Type:Original Article
- Keywords:
Microglia;
BV-2;
RANTES;
LPS;
MAPK;
NF-kB
- MeSH:
Chemokine CCL5*;
Microglia*;
NF-kappa B*;
p38 Mitogen-Activated Protein Kinases*;
Phosphorylation;
Phosphotransferases;
Protein Kinases;
RNA, Messenger;
Second Messenger Systems
- From:The Korean Journal of Physiology and Pharmacology
2000;4(5):339-346
- CountryRepublic of Korea
- Language:English
-
Abstract:
Using murine immortalized microglial cells (BV-2), we examined the regulation of RANTES production stimulated by lipopolysaccharide (LPS), focusing on the role of mitogen-activated protein kinase (MAPK) and nuclear factor (NF)-kappaB. The result showed that RANTES (regulated upon activation of normal T cell expressed and secreted) was induced at the mRNA and protein levels in a dose- and time-dependent manner in response to LPS. From investigations of second messenger pathways involved in regulating the secretion of RANTES, we found that LPS induced phosphorylation of extracellular signal-regulated kinase (Erk), p38 MAPK and c-Jun-N-terminal kinase (JNK), and activated NF-kappaB. To determine whether this MAPK phosphorylation is involved in LPS-stimulated RANTES production, we used specific inhibitors for p38 MAPK and Erk, SB 203580 and PD 98059, respectively. LPS-induced RANTES production was reduced approximately 80% at 25 micrometer of SB 203580 treatment. But PD 98059 did not affect RANTES production. Pyrrolidine-dithiocarbamate (PDTC), NF-kappaB inhibitor, reduced RANTES secretion. These results suggest that LPS-induced RANTES production in microglial cells (BV-2) is mainly mediated by the coordination of p38 MAPK and NF-kappaB cascade.
