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.
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Authors | P Li, J Lu, C Kaur, V Sivakumar, K L Tan, E A Ling |
Journal | Neuroscience
(Neuroscience)
Vol. 164
Issue 3
Pg. 948-62
(Dec 15 2009)
ISSN: 1873-7544 [Electronic] United States |
PMID | 19712723
(Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
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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
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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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