Mitogen-activated protein kinases activated by... : NeuroReport (original) (raw)
Glial Cells
Mitogen-activated protein kinases activated by lipopolysaccharide and β-amyloid in cultured rat microglia
Pyo, Hankyoung1; Jou, Ilo1; Jung, Soyoung1; Hong, Sumin1; Joe, Eun-hye1,2
1Department of Pharmacology, Ajou University School of Medicine, san-5 Woncheon-dong Paldal-gu, Suwon, Kyunggi-do, Korea 442–749
2Corresponding Author: Eun-hye Joe
ACKNOWLEDGEMENTS: This work was supported by BM 97–109 to E.H.J.
Received 17 December 1997;
accepted 18 January 1998
Abstract
TO test whether mitogen-activated protein kinases (MAPKs) are involved in microglial activation, pure microglia prepared from 1- to 3-day-old rat brains were activated with either 10 0 ng/ml lipopolysaccharide (LPS) or 5 nM synthetic β-amyloid (Aβ) (25-35). The patterns of MAPK activation following LPS and Aβ treatment were very similar. Three MAPK subtypes, p38, extracellular signal-regulated kinase (ERK) and c-Jun N- terminal kinase/stress-activated protein kinase (JNK/SAPK) were activated within 1 5 min and the activities of p38 and ERK were rapidly reduced to background level within 3 0 min while that of JNK was maintained for over 1 h. Both inhibitors of p38 (SB203580) and ERK pathway (PD098059) reduced LPS-induced nitric oxide (NO) release and A β-induced tumor necrosis factor α-(TNF-α) release. Furthermore, co-treatment of SB203580 and PD098059 additively reduced NO and TNF α-release. These results suggest that MAPK, at least p38 and ERK, mediate LPS-, and Aβ-induced microglial activation.
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