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|Title:||Expression of cyclooxygenase-1/-2, microsomal prostaglandin-E synthase-1 and E-prostanoid receptor 2 and regulation of inflammatory mediators by PGE2in the amoeboid microglia in hypoxic postnatal rats and murine BV-2 cells|
EP2 receptor antagonist
|Citation:||Li, P., Kaur, C., Sivakumar, V., Tan, K.L., Ling, E.A., Lu, J. (2009). Expression of cyclooxygenase-1/-2, microsomal prostaglandin-E synthase-1 and E-prostanoid receptor 2 and regulation of inflammatory mediators by PGE2in the amoeboid microglia in hypoxic postnatal rats and murine BV-2 cells. Neuroscience 164 (3) : 948-962. ScholarBank@NUS Repository. https://doi.org/10.1016/j.neuroscience.2009.08.044|
|Abstract:||This study aimed to investigate the effect of hypoxia on the expression of cyclooxygenase-1 (COX-1), cyclooxygenase-2 (COX-2), microsomal prostaglandin-E synthase (mPGES-1), E-prostanoid receptor 2 (EP2) in microglia; and the roles of EP2-cyclic adenosine monophosphate (cAMP) signaling pathway in the prostaglandin E2 (PGE2) regulation of inflammatory mediators released by hypoxic BV-2 cells. Immunoexpression of COX-1, COX-2, mPGES-1 and EP2 was localized in the amoeboid microglial cells (AMC), a nascent brain macrophage in the developing brain, as confirmed by double labeling with OX-42 and lectin, specific markers of microglia. AMC emitted a more intense immunofluorescence in hypoxic rats when compared with the matching controls. In postnatal rats subjected to hypoxia, mRNA and protein expression levels of COX-1, COX-2 and mPGES-1 along with tumor necrosis factor-α (TNF-α), interleukin-1β (IL-1β), inducible nitric-oxide synthase (iNOS) and PGE2 product in the callosal tissue were significantly increased. The results were shared in the BV-2 cells except for COX-1 mRNA and protein whose levels remained unaltered. Interestingly, treatment with EP2 antagonist AH-6809 resulted in suppression of hypoxia induced EP2, IL-1β and iNOS mRNA and protein expression, TNF-α protein expression and intracellular cAMP level in BV-2 cells. It is suggested that PGE2 may regulate above inflammatory mediators in the activated microglia via EP2-cAMP signaling pathway in hypoxic conditions. © 2009 IBRO.|
|Appears in Collections:||Staff Publications|
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