Published online before print January 26, 2006, doi: 10.1161/01.RES.0000204725.46332.97
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Submitted on September 8, 2005
Revised on November 21, 2005
Accepted on January 12, 2006
Interferon-
Induces Major Histocompatibility Class II Transactivator (CIITA) That Mediates Collagen Repression and Major Histocompatibility Class II Activation by Human Aortic Smooth Muscle Cells
Giovanna Butticè ;
From the Department of Biochemistry, Boston University School of Medicine; and Veterans Affairs Boston Healthcare System, Mass.
* To whom correspondence should be addressed. E-mail: Smith{at}biochem.bumc.bu.edu.
Chronic inflammation in atherosclerosis is responsible for plaque instability through alterations in extracellular matrix. Previously, we demonstrated that major histocompatibility class II (MHC II) transactivator (CIITA) in a complex with regulatory factor for X box 5 (RFX5) is a crucial protein mediating interferon (IFN)-
-induced repression of collagen type I gene transcription in fibroblasts. This article demonstrates that, in smooth muscle cells (SMCs), IFN- dramatically increases the expression of CIITA isoforms III and IV, with no increase in expression of CIITA isoform I. Expression of CIITA III and IV correlates with decreased collagen type I and increased MHC II gene expression. Exogenous expression of CIITA I, III, and IV, in transiently transfected SMCs, represses collagen type I promoters (COL1A1 and COL1A2) and activates MHC II promoter. Levels of CIITA and RFX5 increase in the nucleus of cells treated with IFN-. Moreover, simvastatin lowers the IFN--induced expression of RFX5 and MHC II in addition to repressing collagen expression. However, simvastatin does not block the IFN--induced expression of CIITA III and IV, suggesting a CIITA-independent mechanism. This first demonstration that RFX5 and CIITA isoforms are expressed in SMCs after IFN- stimulation suggest that CIITA could be a key factor in plaque stability in atherosclerosis.
Key words: collagen • CIITA isoform • RFX • MHC II • SMCs
Related Article:
- Smooth Muscle Cell: A Key Cell for Plaque Vulnerability Regulation?
- Marie-Luce Bochaton-Piallat and Giulio Gabbiani
Circ. Res. 2006 98: 448-449.[Extract] [Full Text] [PDF]
This article has been cited by other articles:
 |
|
 |
|
  X. Wu, X. Kong, L. Luchsinger, B. D. Smith, and Y. Xu Regulating the Activity of Class II Transactivator by Posttranslational Modifications: Exploring the Possibilities Mol. Cell. Biol., November 1, 2009; 29(21): 5639 - 5644. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 I. E. Dumitriu, E. T. Araguas, C. Baboonian, and J. C. Kaski CD4+CD28null T cells in coronary artery disease: when helpers become killers Cardiovasc Res, January 1, 2009; 81(1): 11 - 19. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
C. Rodriguez, J. Martinez-Gonzalez, B. Raposo, J. F. Alcudia, A. Guadall, and L. Badimon Regulation of lysyl oxidase in vascular cells: lysyl oxidase as a new player in cardiovascular diseases Cardiovasc Res, July 1, 2008; 79(1): 7 - 13. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 Y. Xu, K. Ravid, and B. D. Smith Major Histocompatibility Class II Transactivator Expression in Smooth Muscle Cells from A2b Adenosine Receptor Knock-out Mice: CROSS-TALK BETWEEN THE ADENOSINE AND INTERFERON-{gamma} SIGNALING J. Biol. Chem., May 23, 2008; 283(21): 14213 - 14220. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
Y. Xu, J. A. Harton, and B. D. Smith CIITA Mediates Interferon-{gamma} Repression of Collagen Transcription through Phosphorylation-dependent Interactions with Co-repressor Molecules J. Biol. Chem., January 18, 2008; 283(3): 1243 - 1256. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
Y. Xu, S. R. Farmer, and B. D. Smith Peroxisome Proliferator-activated Receptor {gamma} Interacts with CIITA{middle dot}RFX5 Complex to Repress Type I Collagen Gene Expression J. Biol. Chem., September 7, 2007; 282(36): 26046 - 26056. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 I. Gotsman and A. H. Lichtman Targeting Interferon-{gamma} to Treat Atherosclerosis Circ. Res., August 17, 2007; 101(4): 333 - 334. [Full Text] [PDF]
|
|
|
|
|
|
M.-L. Bochaton-Piallat and G. Gabbiani Smooth Muscle Cell: A Key Cell for Plaque Vulnerability Regulation? Circ. Res., March 3, 2006; 98(4): 448 - 449. [Full Text] [PDF]
|
|