Expression of cyclooxygenase-1/-2, microsomal prostaglandin-E synthase-1 and E-prostanoid receptor 2 and regulation of inflammatory mediators by PGE(2) in the amoeboid microglia in hypoxic postnatal rats and murine BV-2 cells.
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 E(2) (PGE(2)) 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-alpha (TNF-alpha), interleukin-1beta (IL-1beta), inducible nitric-oxide synthase (iNOS) and PGE(2) 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-1beta and iNOS mRNA and protein expression, TNF-alpha protein expression and intracellular cAMP level in BV-2 cells. It is suggested that PGE(2) may regulate above inflammatory mediators in the activated microglia via EP2-cAMP signaling pathway in hypoxic conditions.
Li
P
P
Department of Histology and Embryology, Kunming Medical College, 191 West Renmin Road, PR China.
Lu
J
J
Kaur
C
C
Sivakumar
V
V
Tan
K L
KL
Ling
E A
EA
D000818:Animals; D000831:Animals, Newborn; D039481:CD11b Antigen / Q000378:metabolism; D002460:Cell Line; D002465:Cell Movement / Q000502:physiology; D002470:Cell Survival / Q000502:physiology; D000242:Cyclic AMP / Q000378:metabolism; D016207:Cytokines / Q000378:metabolism; D015232:Dinoprostone / Q000378:metabolism*; D004195:Disease Models, Animal; D004660:Encephalitis / Q000378:metabolism* / Q000503:physiopathology; D002534:Hypoxia, Brain / Q000378:metabolism* / Q000503:physiopathology; D019746:Intramolecular Oxidoreductases / Q000235:genetics / Q000378:metabolism*; D051379:Mice; D017628:Microglia / Q000378:metabolism / Q000648:ultrastructure; D008861:Microsomes / Q000378:metabolism / Q000648:ultrastructure; D052247:Nitric Oxide Synthase Type II / Q000378:metabolism; D011448:Prostaglandin Antagonists / Q000494:pharmacology; D000071876:Prostaglandin-E Synthases; D011451:Prostaglandin-Endoperoxide Synthases / Q000235:genetics / Q000378:metabolism*; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D018078:Receptors, Prostaglandin E / Q000378:metabolism*; D058307:Receptors, Prostaglandin E, EP2 Subtype; D015398:Signal Transduction / Q000502:physiology; D044004:Xanthones / Q000494:pharmacology
D039481:CD11b Antigen; D016207:Cytokines; C509295:ITGAM protein, human; C545644:PTGER2 protein, human; D011448:Prostaglandin Antagonists; C545645:Ptger2 protein, mouse; D012333:RNA, Messenger; D018078:Receptors, Prostaglandin E; D058307:Receptors, Prostaglandin E, EP2 Subtype; D044004:Xanthones; C053876:6-isopropoxy-9-oxoxanthene-2-carboxylic acid; D000242:Cyclic AMP; D052247:Nitric Oxide Synthase Type II; D011451:Prostaglandin-Endoperoxide Synthases; D019746:Intramolecular Oxidoreductases; C000605862:PTGES protein, human; D000071876:Prostaglandin-E Synthases; C000605865:Ptges protein, mouse; D015232:Dinoprostone