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KMID : 0811720000040050339
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Korean Journal of Physiology & Pharmacology
2000 Volume.4 No. 5 p.339 ~ p.376
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p38 MAPK and NF-κB are Required for LPS-Induced RANTES Production in Immortalized Murine Microglia (BV-2)
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Kweon-Haeng Lee/Sae-Byeol Jang
Kweon-Haeng Lee
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Abstract
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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)?κB. 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)?κB. 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 25μM of SB 203580 treatment. But PD 98059 did not affect RANTES production. Pyrrolidine-dithiocarbamate (PDTC), (NF)?κB 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)?κB cascade.
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KEYWORD
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Microglia, BV-2, RANTES, LPS, MAPK, NF-κB,
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