View : 11 Download: 0

Selective modulation of lipopolysaccharide-stimulated cytokine expression and mitogen-activated protein kinase pathways by dibutyryl-cAMP in BV2 microglial cells

Title
Selective modulation of lipopolysaccharide-stimulated cytokine expression and mitogen-activated protein kinase pathways by dibutyryl-cAMP in BV2 microglial cells
Authors
Woo M.-S.Jang P.-G.Park J.-S.Kim W.-K.Joh T.H.Kim H.-S.
Ewha Authors
김희선박진선
SCOPUS Author ID
김희선scopus; 박진선scopus
Issue Date
2003
Journal Title
Molecular Brain Research
ISSN
0169-328XJCR Link
Citation
vol. 113, no. 1-2, pp. 86 - 96
Indexed
SCOPUS WOS scopus
Abstract
Cyclic AMP is a very important regulator in a wide range of biological processes, including inflammatory reactions. To investigate the role of cAMP in microglia, we examined the effect of dibutyryl-cAMP (dbcAMP) on lipopolysaccharide (LPS)-stimulated cytokine expression and signaling pathways in murine BV2 microglial cells. DbcAMP strongly suppressed LPS-induced TNF-α expression, without affecting NO, IL-6 or TGF-β1 expression. In contrast, LPS-induced IL-1β or IL-10 expressions were dramatically increased by dbcAMP. We further examined the effect of elevated cAMP on signaling molecules such as MAP kinases (p38 MAPK, ERK and JNK), NF-κB and AP1, which are involved in the regulation of inflammatory responses. DbcAMP decreased the LPS-induced phosphorylation of p38 MAPK, while it modestly enhanced the ERK activity. JNK phosphorylation was slightly reduced by dbcAMP only at the later time point. Electrophoretic mobility shift assay revealed that the elevated cAMP potentiated AP-1 binding activity by enhancing c-fos binding. On the other hand, dbcAMP repressed NF-κB-mediated transcription without affecting NF-κB binding. Treatment with H89, a selective inhibitor of protein kinase A, completely reversed cAMP-induced IL-10 and IL-1β upregulation but only partially reversed the cAMP-induced repression of TNF-α. Thus, the effect of dbcAMP in BV2 cells appears to be mediated through both protein kinase A-dependent and -independent pathways. Taken together, our results demonstrate that cAMP modulates microglia activation in a diverse and complex manner. © 2003 Elsevier Science B.V. All rights reserved.
DOI
10.1016/S0169-328X(03)00095-0
Appears in Collections:
의학전문대학원 > 의학과 > Journal papers
Files in This Item:
There are no files associated with this item.
Export
RIS (EndNote)
XLS (Excel)
XML


qrcode

Items in DSpace are protected by copyright, with all rights reserved, unless otherwise indicated.

BROWSE