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15-deoxy-Δ12,14-prostaglandin J2 inhibits human immunodeficiency virus-1 tat-induced monocyte chemoattractant protein-1/CCL2 production by blocking the extracellular signal-regulated kinase-1/2 signaling pathway independently of peroxisome proliferator-activated receptor-γ and heme oxygenase-1 in rat hippocampal slices

Title
15-deoxy-Δ12,14-prostaglandin J2 inhibits human immunodeficiency virus-1 tat-induced monocyte chemoattractant protein-1/CCL2 production by blocking the extracellular signal-regulated kinase-1/2 signaling pathway independently of peroxisome proliferator-activated receptor-γ and heme oxygenase-1 in rat hippocampal slices
Authors
Kim S.E.Lee E.O.Yang J.H.Kang J.H.L.Suh Y.-H.Chong Y.H.
Ewha Authors
이지희정영해
SCOPUS Author ID
이지희scopus; 정영해scopus
Issue Date
2012
Journal Title
Journal of Neuroscience Research
ISSN
0360-4012JCR Link
Citation
vol. 90, no. 9, pp. 1732 - 1742
Indexed
SCI; SCIE; SCOPUS WOS scopus
Abstract
Human immunodeficiency virus (HIV)-induced inflammation, and its consequences within the central nervous system (CNS), must be countered by multiple pharmacologic agents, and 15-deoxy-Δ12,14-prostaglandin J2 (15d-PGJ2) may hold promise in the treatment of pathologies associated with this inflammatory response. 15d-PGJ2 can repress the inflammatory response by means of peroxisome proliferator-activated receptor-γ (PPARγ)-dependent and -independent mechanisms. However, its precise role and antiinflammatory mechanism in the hippocampus remain poorly understood. In the present study, rat hippocampal slices were stimulated with full-length HIV-1 Tat protein to investigate the role of 15d-PGJ2 8in the hippocampal inflammatory response. Pretreatment of slices with 15d-PGJ2 markedly reduced Tat-induced monocyte chemoattractant protein-1 (MCP-1/CCL2) production. Interestingly, the PPARγ antagonist GW9662 did not inhibit action of 15d-PGJ2, confirming the latter's PPARγ-independent mechanism of mediating antiinflammatory effects. Despite 15d-PGJ2's increasing the expression of heme oxygenase-1 (HO-1), its action was not abrogated by the HO-1 inhibitor zinc protoporphyrin IX (ZnPPIX), nor was it recapitulated by HO-1 inducers such as cobalt protoporphyrin (CoPP). Moreover, short interfering RNA (siRNA)-directed knockdown of HO-1 did not abolish the antiinflammatory action of 15d-PGJ2 against Tat-induced MCP-1 production in human microglia-like THP-1 cells. Conversely, 15d-PGJ2 suppressed Tat-induced ERK1/2 activation, decreasing MCP-1 production upon Tat stimulation. The NADPH oxidase inhibitors DPI and apocynin also abrogated Tat-stimulated ERK1/2 activation, reducing MCP-1 production. Collectively, these data demonstrate that the antiinflammatory effects of 15d-PGJ2 on the hippocampus are exerted through inhibition of Tat-mediated ERK1/2 activation, coupled with that of a redox-sensitive pathway, independent of PPARγ and HO-1. © 2012 Wiley Periodicals, Inc.
DOI
10.1002/jnr.23051
Appears in Collections:
의과대학 > 의학과 > Journal papers
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