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Uridine 5'-diphosphate induces chemokine expression in microglia and astrocytes through activation of the P2Y6 receptor

DC Field Value Language
dc.contributor.authorKim, B-
dc.contributor.authorJeong, HK-
dc.contributor.authorKim, JH-
dc.contributor.authorLee, SY-
dc.contributor.authorJou, I-
dc.contributor.authorJoe, EH-
dc.date.accessioned2012-03-29-
dc.date.available2012-03-29-
dc.date.issued2011-
dc.identifier.issn0022-1767-
dc.identifier.urihttp://repository.ajou.ac.kr/handle/201003/6349-
dc.description.abstractChemokines play critical roles in inflammation by recruiting inflammatory cells to injury sites. In this study, we found that UDP induced expression of chemokines CCL2 (MCP-1) and CCL3 (MIP-1α) in microglia, astrocytes, and slice cultures by activation of P2Y(6). Interestingly, CCL2 was more highly expressed than CCL3. However, CCL2 synthesis kinetics in response to UDP differed in microglia and astrocytes; microglia rapidly produced small amounts of CCL2, whereas astrocytes continuously synthesized large amounts of CCL2, resulting in a high ultimate level of the chemokine. UDP-induced chemokine expression was reduced in the presence of a specific antagonist of P2Y(6) (MRS2578) or small interfering RNA directed against the P2Y(6) gene. Inhibition of phospholipase C and calcium increase, downstream signaling pathways of Gq-coupled P2Y(6), reduced UDP-induced chemokine expression. UDP activated two calcium-activated transcription factors, NFATc1 and c2. Furthermore, inhibitors of calcineurin (a phosphatase activating NFAT) and NFAT reduced UDP-induced chemokine synthesis. We also found, using a transmigration assay, that UDP-treated astrocytes recruited monocytes. These results suggest that UDP induces chemokine expression in microglia and astrocytes of the injured brain by activation of P2Y(6) receptors.-
dc.language.isoen-
dc.subject.MESHAnimals-
dc.subject.MESHAnimals, Newborn-
dc.subject.MESHAstrocytes-
dc.subject.MESHCell Movement-
dc.subject.MESHCells, Cultured-
dc.subject.MESHCerebral Cortex-
dc.subject.MESHChemokine CCL2-
dc.subject.MESHChemokine CCL3-
dc.subject.MESHMicroglia-
dc.subject.MESHMonocytes-
dc.subject.MESHOrgan Culture Techniques-
dc.subject.MESHRats-
dc.subject.MESHRats, Sprague-Dawley-
dc.subject.MESHReceptors, Purinergic P2-
dc.subject.MESHUridine Diphosphate-
dc.titleUridine 5'-diphosphate induces chemokine expression in microglia and astrocytes through activation of the P2Y6 receptor-
dc.typeArticle-
dc.identifier.pmid21317391-
dc.identifier.urlhttp://www.jimmunol.org/cgi/pmidlookup?view=long&pmid=21317391-
dc.contributor.affiliatedAuthor김, 범수-
dc.contributor.affiliatedAuthor이, 상윤-
dc.contributor.affiliatedAuthor주, 일로-
dc.contributor.affiliatedAuthor조, 은혜-
dc.type.localJournal Papers-
dc.identifier.doi10.4049/jimmunol.1000212-
dc.citation.titleJournal of immunology (Baltimore, Md. : 1950)-
dc.citation.volume186-
dc.citation.number6-
dc.citation.date2011-
dc.citation.startPage3701-
dc.citation.endPage3709-
dc.identifier.bibliographicCitationJournal of immunology (Baltimore, Md. : 1950), 186(6). : 3701-3709, 2011-
dc.identifier.eissn1550-6606-
dc.relation.journalidJ000221767-
Appears in Collections:
Journal Papers > School of Medicine / Graduate School of Medicine > Pharmacology
Journal Papers > Research Organization > Institute for Medical Sciences
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