| Nuclear receptor Nur77 suppresses inflammatory response dependent on COX-2 in macrophages induced by oxLDL. | |
| | |
MedLine Citation:
|
PMID: 20381497 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
|
Oxidized low-density lipoprotein (oxLDL) cross-talks with macrophages, and both play a crucial role in the initiation and progression of atherosclerosis. Orphan nuclear receptor Nur77 is potently induced in macrophages by diverse stimuli, suggesting that it may be a key regulator of inflammation in vascular cells. The detailed mechanism of Nur77 activation and subsequent function in macrophages induced by oxLDL remains unclearly. In this study, we demonstrated that Nur77 is upregulated in a dose and time-dependent fashion by oxLDL stimulation in murine macrophages, as detected by real-time PCR and Western blotting. OxLDL activated the phosphorylation ERK1/2 and p38 MAPK, inhibition of p38 MAPK but not ERK1/2 attenuated Nur77 expression. Importantly, overexpression of Nur77 suppressed oxLDL-induced proinflammatory cytokines and chemokines secretion including tumor necrosis factor (TNF)alpha and monocyte chemoattractant protein-1(MCP-1). While knockdown Nur77 expression by specific small interfering RNA (siRNA) resulted in the enhancement of the secretion. Furthermore, exposure of macrophages to oxLDL significantly upregulated cyclooxygenase-2(COX-2) expression. However, this could be markedly inhibited by Nur77 overexpression. Also, Nur77 siRNA increased oxLDL-induced COX-2 expression and 6-mercaptopurine (6-MP) attenuated the increase. The results indicated that Nur77 is induced by oxLDL via p38 MAPK signal pathway and subsequently protects against inflammation by the inhibition of proinflammatory COX-2 pathway in activated macrophages. Specifically modifying transcription activity of Nur77 may represent a potential molecular target for the prevention and treatment of atherosclerosis. |
| | |
Authors:
|
Qin Shao; Ling-Hong Shen; Liu-Hua Hu; Jun Pu; Mei-Yan Qi; Wen-Qing Li; Fu-Ju Tian; Qing Jing; Ben He |
Related Documents
:
|
6340837 - Human t-cell hybridomas producing lymphokines. ii. enhancement of lymphotoxin secretion... 10398027 - Chemotaxis and activation of particle-challenged human monocytes in response to monocyt... 10938017 - Oxidized ldl-induced nf-kappa b activation and subsequent expression of proinflammatory... 14620137 - Macrophage migration inhibitory factor and host innate immune responses to microbes. 11809367 - Green tea polyphenols: dna photodamage and photoimmunology. 19098237 - The immunomodulatory effect of lactulose on enterococcus faecium fed preruminant calves. |
Publication Detail:
|
Type: Journal Article; Research Support, Non-U.S. Gov't Date: 2010-04-08 |
Journal Detail:
|
Title: Journal of molecular and cellular cardiology Volume: 49 ISSN: 1095-8584 ISO Abbreviation: J. Mol. Cell. Cardiol. Publication Date: 2010 Aug |
Date Detail:
|
Created Date: 2010-06-14 Completed Date: 2010-09-09 Revised Date: - |
Medline Journal Info:
|
Nlm Unique ID: 0262322 Medline TA: J Mol Cell Cardiol Country: England |
Other Details:
|
Languages: eng Pagination: 304-11 Citation Subset: IM |
Affiliation:
|
Department of Cardiology, Medical School of Shanghai Jiao Tong University, Shanghai, People's Republic of China. |
Export Citation:
|
APA/MLA Format Download EndNote Download BibTex |
| MeSH Terms | |
Descriptor/Qualifier:
|
Animals Cell Line Chemokines / metabolism Cyclooxygenase 2 / genetics, metabolism* Cyclooxygenase Inhibitors / pharmacology Humans Inflammation / enzymology* Lipoproteins, LDL / pharmacology* Macrophages / drug effects, enzymology*, pathology* Mice Nuclear Receptor Subfamily 4, Group A, Member 1 / genetics, metabolism* Up-Regulation / drug effects p38 Mitogen-Activated Protein Kinases / metabolism |
| Chemical | |
Reg. No./Substance:
|
0/Chemokines; 0/Cyclooxygenase Inhibitors; 0/Lipoproteins, LDL; 0/Nr4a1 protein, mouse; 0/Nuclear Receptor Subfamily 4, Group A, Member 1; 0/oxidized low density lipoprotein; EC 1.14.99.-/Ptgs2 protein, mouse; EC 1.14.99.1/Cyclooxygenase 2; EC 2.7.11.24/p38 Mitogen-Activated Protein Kinases |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
Previous Document: Quantification of circulating endothelial progenitor cells in human peripheral blood: Establishing a...
Next Document: Functional states of homooligomers: insights from the evolution of glycosyltransferases.