The effects of inflammatory cytokines on steroidogenic acute regulatory protein expression in macrophages

被引:39
作者
Ma, Y. [1 ]
Ren, S. [2 ]
Pandak, W. M. [2 ]
Li, X. [1 ]
Ning, Y. [1 ]
Lu, C. [1 ]
Zhao, F. [1 ]
Yin, L. [1 ]
机构
[1] Fudan Univ, Shaghai Med Coll, Dept Physiol & Pathophysiol, Shanghai 200032, Peoples R China
[2] Virginia Commonwealth Univ, VA Med Ctr, Dept Med, Richmond, VA 23298 USA
基金
中国国家自然科学基金;
关键词
steroidogenic acute regulatory protein; tumor necrosis factor-alpha; interferon-gamma; transforming growth factor-beta1;
D O I
10.1007/s00011-007-6133-3
中图分类号
Q2 [细胞生物学];
学科分类号
071009 [细胞生物学]; 090102 [作物遗传育种];
摘要
Objective: To investigate the expression of steroidogenic acute regulatory protein (StAR) in macrophages and the effects of inflammatory cytokines on StAR expression. Methods: The macrophages isolated from ApoE knockout mice and C57BL/6J mice and RAW264.7 cells (a cell line from mouse macrophage. ATCC Number: TIB-71 (TM)) were cultured in DMEM containing 10% fetal bovine serum. RAW264.7 cells were treated with different inflammatory cytokines (TNF-alpha, IFN-gamma and TGF-beta 1) and 8-Br-cAMP, a cAMP analog. RT-PCR and Western blot analysis were applied to evaluate the effects of inflammatory cytokines on StAR expression. Results: RT-PCR and Western blot analysis demonstrated the expression of StAR in the macrophages isolated from ApoE knockout mice, C57BL/6J mice and RAW264.7 cells. Pro-inflammatory cytokines TNF-alpha and IFN-gamma significantly decreased StAR mRNA and protein levels in RAW264.7 cells. The inhibition was dose- and time-dependent. In contrast, anti-inflammatory cytokine TGF-beta 1 increased StAR mRNA and protein levels. At 1: 15 molecular ratio, TGF-beta 1 blocked the down-regulation of StAR expression mediated by TNF-alpha. cAMP also induced StAR expression in RAW264.7 cells. When the cells were co-treated with 8-Br-cAMP and TNF-alpha, 8-Br-cAMP failed to induce StAR expression. Conclusion: Our results provide interesting evidence that inflammatory cytokines regulate StAR expression in macrophages.
引用
收藏
页码:495 / 501
页数:7
相关论文
共 27 条
[1]
Elimination of cholesterol in macrophages and endothelial cells by the sterol 27-hydroxylase mechanism - Comparison with high density lipoprotein-mediated reverse cholesterol transport [J].
Babiker, A ;
Andersson, O ;
Lund, E ;
Xiu, RJ ;
Deeb, S ;
Reshef, A ;
Leitersdorf, E ;
Diczfalusy, U ;
Bjorkhem, I .
JOURNAL OF BIOLOGICAL CHEMISTRY, 1997, 272 (42) :26253-26261
[2]
Smad3 is involved in the intracellular signaling pathways that mediate the inhibitory effects of transforming growth factor-β on StAR expression [J].
Brand, C ;
Souchelnytskiy, S ;
Chambaz, EM ;
Feige, JJ ;
Bailly, S .
BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS, 1998, 253 (03) :780-785
[3]
Transforming growth factor β1 decreases cholesterol supply to mitochondria via repression of steroidogenic acute regulatory protein expression [J].
Brand, C ;
Cherradi, N ;
Defaye, G ;
Chinn, A ;
Chambaz, EM ;
Feige, JJ ;
Bailly, S .
JOURNAL OF BIOLOGICAL CHEMISTRY, 1998, 273 (11) :6410-6416
[4]
Steroidogenic acute regulatory protein (StAR) and the intramitochondrial translocation of cholesterol [J].
Christenson, LK ;
Strauss, JF .
BIOCHIMICA ET BIOPHYSICA ACTA-MOLECULAR AND CELL BIOLOGY OF LIPIDS, 2000, 1529 (1-3) :175-187
[5]
Localization of sterol 27-hydroxylase immuno-reactivity in human atherosclerotic plaques [J].
Crisby, M ;
Nilsson, J ;
Kostulas, V ;
Bjorkhem, I ;
Diczfalusy, U .
BIOCHIMICA ET BIOPHYSICA ACTA-LIPIDS AND LIPID METABOLISM, 1997, 1344 (03) :278-285
[6]
Expression of sterol 27-hydroxylase (CYP27A1) enhances cholesterol efflux [J].
Escher, G ;
Krozowski, Z ;
Croft, KD ;
Sviridov, D .
JOURNAL OF BIOLOGICAL CHEMISTRY, 2003, 278 (13) :11015-11019
[7]
27-hydroxycholesterol is an endogenous ligand for liver X receptor in cholesterol-loaded cells [J].
Fu, X ;
Menke, JG ;
Chen, YL ;
Zhou, GC ;
MacNaul, KL ;
Wright, SD ;
Sparrow, CP ;
Lund, EG .
JOURNAL OF BIOLOGICAL CHEMISTRY, 2001, 276 (42) :38378-38387
[8]
Detection of the steroidogenic acute regulatory protein, StAR, in human liver cells [J].
Hall, EA ;
Ren, S ;
Hylemon, PB ;
Rodriguez-Agudo, D ;
Redford, K ;
Marques, D ;
Kang, D ;
Gil, G ;
Pandak, WM .
BIOCHIMICA ET BIOPHYSICA ACTA-MOLECULAR AND CELL BIOLOGY OF LIPIDS, 2005, 1733 (2-3) :111-119
[9]
Regulation of sterol 27-hydroxylase in human monocyte-derived macrophages:: up-regulation by transforming growth factor β1 [J].
Hansson, M ;
Wikvall, K ;
Babiker, A .
BIOCHIMICA ET BIOPHYSICA ACTA-MOLECULAR AND CELL BIOLOGY OF LIPIDS, 2005, 1687 (1-3) :44-51
[10]
MOLECULAR-CLONING AND IN-VIVO EXPRESSION OF THE BOVINE STEROIDOGENIC ACUTE REGULATORY PROTEIN [J].
HARTUNG, S ;
RUST, W ;
BALVERS, M ;
IVELL, R .
BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS, 1995, 215 (02) :646-653