| Induction of Cox-2 and down-regulation of Cox-1 expression by LPS control prostaglandin E2 production in astrocytes. | |
| | |
MedLine Citation:
|
PMID: 22219191 Owner: NLM Status: Publisher |
Abstract/OtherAbstract:
|
Brain pathological conditions and pro-inflammatory stimuli induce cyclooxygenase-2 (COX-2), a key enzyme in arachidonic acid metabolism mediating the production of prostanoids that, amongst other actions, have strong vasoactive properties. Although low basal cerebral COX-2 expression has been reported, COX-2 is strongly induced by pro-inflammatory challenges, whereas COX-1 is constitutively expressed. However, the contribution of these enzymes in prostanoid formation varies depending on the stimuli and cell type. Astrocyte feet surround cerebral microvessels and release molecules that can trigger vascular responses. Here we investigate the regulation of COX-2 induction and its role in prostanoid generation after a pro-inflammatory challenge with the bacterial lypopolysaccharide (LPS) in astroglia. Intracerebral administration of LPS in rodents induced strong COX-2 expression mainly in astroglia and microglia, while COX-1 expression was predominant in microglia, and did not increase. In cultured astrocytes, LPS strongly induced COX-2 and microsomal prostaglandin-E2 (PGE2) synthase-1, mediated by the MyD88-dependent NFκB pathway and influenced by mitogen-activated protein kinase pathways. Studies in COX-deficient cells and using COX inhibitors demonstrated that COX-2 mediated the high production of PGE2 and, to a lesser extent, other prostanoids after LPS. In contrast, LPS down-regulated COX-1 in a MyD88 dependent fashion, and COX-1 deficiency increased PGE2 production after LPS. The results evidence that astrocytes respond to LPS by a COX-2 dependent production of prostanoids, mainly vasoactive PGE2, and suggest that the coordinated down-regulation of COX-1 facilitates PGE2 production after TLR-4 activation. These effects might induce cerebral blood flow responses to brain inflammation. |
| | |
Authors:
|
Miriam Font-Nieves; M Gloria Sans-Fons; Roser Gorina; Ester Bonfill-Teixidor; Angelica Salas-Perdomo; Leonardo Marquez-Kisinousky; Tomas Santalucia; Anna M Planas |
Publication Detail:
|
Type: JOURNAL ARTICLE Date: 2012-1-4 |
Journal Detail:
|
Title: The Journal of biological chemistry Volume: - ISSN: 1083-351X ISO Abbreviation: - Publication Date: 2012 Jan |
Date Detail:
|
Created Date: 2012-1-5 Completed Date: - Revised Date: - |
Medline Journal Info:
|
Nlm Unique ID: 2985121R Medline TA: J Biol Chem Country: - |
Other Details:
|
Languages: ENG Pagination: - Citation Subset: - |
Affiliation:
|
IIBB-CSIC, IDIBAPS, Spain. |
Export Citation:
|
APA/MLA Format Download EndNote Download BibTex |
| MeSH Terms | |
Descriptor/Qualifier:
|
|
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
Previous Document: Biophysical and mechanistic insights into a novel allosteric inhibitor of spleen tyrosine kinase.
Next Document: Composition and dynamics of the nucleolinus, a link between the nucleolus and cell division apparatu...