國家衛生研究院 NHRI:Item 3990099045/1284
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    题名: TNF-alpha/IFN-gamma-induced iNOS expression increased by prostaglandin E-2 in rat primary astrocytes via EP2-evoked cAMP/PKA and intracellular calcium signaling
    其它题名: TNF-α/IFN-γ-induced iNOS expression increased by prostaglandin E2 in rat primary astrocytes via EP2-evoked cAMP/PKA and intracellular calcium signaling
    作者: Hsiao, HY;Mak, OT;Yang, CS;Liu, YP;Fang, KM;Tzeng, SF
    贡献者: Center for Nanomedicine Research
    摘要: Astrocytes, the most abundant glia in the central nervous system (CNS), produce a large amount of prostaglandin E-2 (PGE(2)) in response to proinflammatory mediators after CNS injury. However, it is unclear whether PGE2 has a regulatory role in astrocytic activity under the inflamed condition. In the present work, we showed that PGE2 increased inducible nitric oxide synthase (iNOS) production by tumor necrosis factor-et and interferon-gamma (T/I) in astrocytes. Pharmacological and RNA interference approaches further indicated the involvement of the receptor EP2 in PGE(2)-induced iNOS upregulation in T/I-treated astrocytes. Quantitative real-time polymerase chain reaction and gel mobility shift assays also demonstrated that PGE2 increased iNOS transcription through EP2-induced cAMP/protein kinase A (PYA)-dependent pathway. Consistently, the effect of EP2 was significantly attenuated by the PKA inhibitor KT-5720 and partially suppressed by the inhibitor (SB203580) of p38 mitogen-activated protein kinase (p38MAPK), which serves as one of the downstream components of the PKA-dependent pathway. Interestingly, EP2-mediated PKA signaling appeared to increase intracellular Ca2+ release through inositol triphosphate (IP3) receptor activation, which might in turn stimulate protein kinase C (PKC) activation to promote iNOS production in T/I-primed astrocytes. By analyzing the expression of astrocytic glial fibrillary acidic protein (GFAP), we found that PGE(2) alone only triggered the EP2-induced cAMP/PKA/p38MAPK signaling pathway in astrocytes. Collectively, PGE2 may enhance T/I-induced astrocytic activation by augmenting iNOS/NO production through EP2-mediated cross-talk between cAMP/PKA and IP3/Ca2+ signaling pathways.
    关键词: Neurosciences
    日期: 2007-01-15
    關聯: Glia. 2007 Jan;55(2):214-223.
    Link to: http://dx.doi.org/10.1002/glia.20453
    JIF/Ranking 2023: http://gateway.webofknowledge.com/gateway/Gateway.cgi?GWVersion=2&SrcAuth=NHRI&SrcApp=NHRI_IR&KeyISSN=0894-1491&DestApp=IC2JCR
    Cited Times(WOS): https://www.webofscience.com/wos/woscc/full-record/WOS:000242629000009
    Cited Times(Scopus): http://www.scopus.com/inward/record.url?partnerID=HzOxMe3b&scp=33845914958
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