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

Moon Sook Woo, Pil Geum Jang, Jin Sun Park, Won Ki Kim, Tong H. Joh, Hee Sun Kim

Research output: Contribution to journalArticle

66 Citations (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.

Original languageEnglish
Pages (from-to)86-96
Number of pages11
JournalMolecular Brain Research
Volume113
Issue number1-2
DOIs
Publication statusPublished - 2003 May 12
Externally publishedYes

Keywords

  • Cytokines
  • MAP kinases
  • Microglia
  • Protein kinase A
  • Transcription factors
  • dbcAMP

ASJC Scopus subject areas

  • Molecular Biology
  • Cellular and Molecular Neuroscience

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