PMID- 20381497
OWN - NLM
STAT- MEDLINE
DCOM- 20100909
LR  - 20100614
IS  - 1095-8584 (Electronic)
IS  - 0022-2828 (Linking)
VI  - 49
IP  - 2
DP  - 2010 Aug
TI  - Nuclear receptor Nur77 suppresses inflammatory response dependent on COX-2 in 
      macrophages induced by oxLDL.
PG  - 304-11
LID - 10.1016/j.yjmcc.2010.03.023 [doi]
AB  - 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.
FAU - Shao, Qin
AU  - Shao Q
AD  - Department of Cardiology, Medical School of Shanghai Jiao Tong University, 
      Shanghai, People's Republic of China.
FAU - Shen, Ling-Hong
AU  - Shen LH
FAU - Hu, Liu-Hua
AU  - Hu LH
FAU - Pu, Jun
AU  - Pu J
FAU - Qi, Mei-Yan
AU  - Qi MY
FAU - Li, Wen-Qing
AU  - Li WQ
FAU - Tian, Fu-Ju
AU  - Tian FJ
FAU - Jing, Qing
AU  - Jing Q
FAU - He, Ben
AU  - He B
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20100408
PL  - England
TA  - J Mol Cell Cardiol
JT  - Journal of molecular and cellular cardiology
JID - 0262322
RN  - 0 (Chemokines)
RN  - 0 (Cyclooxygenase Inhibitors)
RN  - 0 (Lipoproteins, LDL)
RN  - 0 (Nr4a1 protein, mouse)
RN  - 0 (Nuclear Receptor Subfamily 4, Group A, Member 1)
RN  - 0 (oxidized low density lipoprotein)
RN  - EC 1.14.99.- (Ptgs2 protein, mouse)
RN  - EC 1.14.99.1 (Cyclooxygenase 2)
RN  - EC 2.7.11.24 (p38 Mitogen-Activated Protein Kinases)
SB  - IM
MH  - Animals
MH  - Cell Line
MH  - Chemokines/metabolism
MH  - Cyclooxygenase 2/genetics/*metabolism
MH  - Cyclooxygenase Inhibitors/pharmacology
MH  - Humans
MH  - Inflammation/*enzymology
MH  - Lipoproteins, LDL/*pharmacology
MH  - Macrophages/drug effects/*enzymology/*pathology
MH  - Mice
MH  - Nuclear Receptor Subfamily 4, Group A, Member 1/genetics/*metabolism
MH  - Up-Regulation/drug effects
MH  - p38 Mitogen-Activated Protein Kinases/metabolism
EDAT- 2010/04/13 06:00
MHDA- 2010/09/10 06:00
CRDT- 2010/04/13 06:00
PHST- 2010/01/09 00:00 [received]
PHST- 2010/03/29 00:00 [revised]
PHST- 2010/03/30 00:00 [accepted]
PHST- 2010/04/13 06:00 [entrez]
PHST- 2010/04/13 06:00 [pubmed]
PHST- 2010/09/10 06:00 [medline]
AID - S0022-2828(10)00133-1 [pii]
AID - 10.1016/j.yjmcc.2010.03.023 [doi]
PST - ppublish
SO  - J Mol Cell Cardiol. 2010 Aug;49(2):304-11. doi: 10.1016/j.yjmcc.2010.03.023. Epub 
      2010 Apr 8.