Reciprocal regulation of ATPγS-induced monocyte chemoattractant protein-1 production by ERK and p38 MAP kinasesin rat corticostriatal slice cultures

Takahiro Katayama, Misato Ito, Shuji Kaneko, Masamichi Satoh, Takashi Uehara, Masabumi Minami

Research output: Contribution to journalArticle

7 Citations (Scopus)

Abstract

Monocyte chemoattractant protein-1 (MCP-1, CCL2) is a well-defined chemokine implicated in the pathology of various neurodegenerative diseases and brain injuries, such as Alzheimer's disease, multiple sclerosis, stroke, and traumatic injury. We investigated the effect of the activation of P2 purinoceptors on MCP-1 production in rat corticostriatal slice cultures. Treatment with adenosine 5′-O-(3-thiotriphosphate) (ATPγS), a hydrolysis-resistant adenosine triphosphate (ATP) analog, induced MCP-1 production in astrocytes. The induction was in a concentration-dependent manner and was antagonized by a P2 purinoceptor antagonist pyridoxal phosphate-6-azophenyl-2′,4′-disulfonic acid. The inhibition of an extracellular signal-regulated kinase (ERK) pathway by PD98059 and U0126 significantly suppressed ATPγS-induced MCP-1 mRNA expression and protein production, while inhibition of c-Jun N-terminal kinase by SP600125 resulted in the partial suppression. Conversely, SB203580, a p38 mitogen-activated protein (MAP) kinase inhibitor, significantly enhanced ATPγS-induced MCP-1 production. Similar effects of ERK and p38 MAP kinase inhibitors on MCP-1 production were observed in the slices stimulated by ATP and BzATP. These results demonstrate that astrocytic MCP-1 production induced by P2 purinoceptor stimulation is reciprocally regulated by ERK and p38 MAP kinases in the organotypic slice cultures.

Original languageEnglish
Pages (from-to)1573-1581
Number of pages9
JournalJournal of Neuroscience Research
Volume87
Issue number7
DOIs
Publication statusPublished - May 15 2009
Externally publishedYes

Keywords

  • ATP
  • Astrocyte
  • Chemokine
  • MCP-1
  • Organotypic slice culture

ASJC Scopus subject areas

  • Cellular and Molecular Neuroscience

Fingerprint Dive into the research topics of 'Reciprocal regulation of ATPγS-induced monocyte chemoattractant protein-1 production by ERK and p38 MAP kinasesin rat corticostriatal slice cultures'. Together they form a unique fingerprint.

  • Cite this