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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.

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 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.
AuthorsP Li, J Lu, C Kaur, V Sivakumar, K L Tan, E A Ling
JournalNeuroscience (Neuroscience) Vol. 164 Issue 3 Pg. 948-62 (Dec 15 2009) ISSN: 1873-7544 [Electronic] United States
PMID19712723 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
Chemical References
  • CD11b Antigen
  • Cytokines
  • ITGAM protein, human
  • PTGER2 protein, human
  • Prostaglandin Antagonists
  • Ptger2 protein, mouse
  • RNA, Messenger
  • Receptors, Prostaglandin E
  • Receptors, Prostaglandin E, EP2 Subtype
  • Xanthones
  • 6-isopropoxy-9-oxoxanthene-2-carboxylic acid
  • Cyclic AMP
  • Nitric Oxide Synthase Type II
  • Prostaglandin-Endoperoxide Synthases
  • Intramolecular Oxidoreductases
  • PTGES protein, human
  • Prostaglandin-E Synthases
  • Ptges protein, mouse
  • Dinoprostone
Topics
  • Animals
  • Animals, Newborn
  • CD11b Antigen (metabolism)
  • Cell Line
  • Cell Movement (physiology)
  • Cell Survival (physiology)
  • Cyclic AMP (metabolism)
  • Cytokines (metabolism)
  • Dinoprostone (metabolism)
  • Disease Models, Animal
  • Encephalitis (metabolism, physiopathology)
  • Hypoxia, Brain (metabolism, physiopathology)
  • Intramolecular Oxidoreductases (genetics, metabolism)
  • Mice
  • Microglia (metabolism, ultrastructure)
  • Microsomes (metabolism, ultrastructure)
  • Nitric Oxide Synthase Type II (metabolism)
  • Prostaglandin Antagonists (pharmacology)
  • Prostaglandin-E Synthases
  • Prostaglandin-Endoperoxide Synthases (genetics, metabolism)
  • RNA, Messenger (metabolism)
  • Rats
  • Receptors, Prostaglandin E (metabolism)
  • Receptors, Prostaglandin E, EP2 Subtype
  • Signal Transduction (physiology)
  • Xanthones (pharmacology)

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