Interferon gamma inhibits both proliferation and expression of differentiation-specific alpha-smooth muscle actin in arterial smooth muscle cells

doi:10.1084/jem.170.5.1595

This Article

	Full Text (PDF, 954K)
	Alert me when this article is cited
	Citation Map

Services

	Email this article
	Similar articles in this journal
	Similar articles in PubMed
	Alert me to new content in the JEM
	Download to citation manager

Citing Articles

	Citing Articles via HighWire
	Citing Articles via CrossRef
	Citing Articles via Google Scholar

Google Scholar

	Articles by Hansson, G. K.
	Articles by Gabbiani, G.
	Search for Related Content

PubMed

	PubMed Citation
	Articles by Hansson, G. K.
	Articles by Gabbiani, G.


Social Bookmarking

	What's this?

ARTICLES

Interferon gamma inhibits both proliferation and expression of differentiation-specific alpha-smooth muscle actin in arterial smooth muscle cells

GK Hansson, M Hellstrand, L Rymo, L Rubbia and G Gabbiani
Department of Clinical Chemistry, Gothenburg University, Sahlgren's Hospital, Sweden.

Differentiation of muscle cells is characterized morphologically by the acquisition of contractile filaments and characteristic shape changes, and on the molecular level by induction of the expression of several genes, including those for the muscle-specific alpha-actin isoforms. IFN-gamma is an inhibitor of proliferation for several cells, including vascular smooth muscle, and is also an inducer of differentiated properties for several hematopoietic cells. We have therefore investigated whether IFN-gamma affects the expression of alpha-smooth muscle actin in cultured arterial smooth muscle cells. Cells exposed to IFN-gamma show a reduction of alpha-smooth muscle actin-containing stress fibers, as detected by immunofluorescence. The effect was observed in all phases of the cell cycle, and was caused by a reduction of the synthesis of alpha-smooth muscle actin protein as revealed by two-dimensional electrophoretic analysis of actin isoforms. RNA hybridization using a cRNA probe that hybridizes to all actin mRNAs showed that IFN-gamma-treated cells have a reduced content of the 1.7- kb mRNA that codes for alpha-smooth muscle actin, and to a lesser extent, also of the 2.1-kb mRNA encoding the beta and gamma-cytoplasmic actins. The reduction of alpha-smooth muscle actin mRNA was confirmed using an alpha-smooth muscle actin-specific cRNA probe. The reduction of alpha-smooth muscle actin mRNA occurs within 12 h, and is dependent on protein synthesis, since cycloheximide treatment reversed the effect. The inhibition of this mRNA species was dose dependent, and detectable by RNA hybridization at a dose of 50 U/ml IFN-gamma. These results suggest that the differentiation of arterial smooth muscle cells is not necessarily coupled to an inhibition of cellular proliferation. Instead, IFN-gamma may regulate the expression of several genes that control both proliferation and expression of differentiation markers.
Add to CiteULike CiteULike Add to Complore Complore Add to Connotea Connotea Add to Del.icio.us Del.icio.us Add to Digg Digg Facebook Add to Reddit Reddit Add to Technorati Technorati Twitter What's this?

This article has been cited by other articles:

Hansson, G. K., Jonasson, L. (2009). The Discovery of Cellular Immunity in the Atherosclerotic Plaque. Arterioscler. Thromb. Vasc. Bio. 29: 1714-1717 [Abstract] [Full Text]
Walcher, D., Hess, K., Berger, R., Aleksic, M., Heinz, P., Bach, H., Durst, R., Hausauer, A., Hombach, V., Marx, N. (2009). Resistin: a newly identified chemokine for human CD4-positive lymphocytes. Cardiovasc Res 0: cvp278v2-cvp278 [Abstract] [Full Text]
Kempe, S., Heinz, P., Kokai, E., Devergne, O., Marx, N., Wirth, T. (2009). Epstein-Barr Virus-Induced Gene-3 Is Expressed in Human Atheroma Plaques. Am. J. Pathol. 175: 440-447 [Abstract] [Full Text]
Ovchinnikova, O., Robertson, A.-K. L., Wagsater, D., Folco, E. J., Hyry, M., Myllyharju, J., Eriksson, P., Libby, P., Hansson, G. K. (2009). T-Cell Activation Leads to Reduced Collagen Maturation in Atherosclerotic Plaques of Apoe-/- Mice. Am. J. Pathol. 174: 693-700 [Abstract] [Full Text]
Tellides, G., Pober, J. S. (2007). Interferon-{gamma} Axis in Graft Arteriosclerosis. Circ. Res. 100: 622-632 [Abstract] [Full Text]
Isobe, M., Kosuge, H., Suzuki, J.-i. (2006). T Cell Costimulation in the Development of Cardiac Allograft Vasculopathy: Potential Targets for Therapeutic Interventions. Arterioscler. Thromb. Vasc. Bio. 26: 1447-1456 [Abstract] [Full Text]
Pacifico, L., Di Renzo, L., Anania, C., Osborn, J. F, Ippoliti, F., Schiavo, E., Chiesa, C. (2006). Increased T-helper interferon-{gamma}-secreting cells in obese children.. Eur J Endocrinol 154: 691-697 [Abstract] [Full Text]
Walcher, D., Kummel, A., Kehrle, B., Bach, H., Grub, M., Durst, R., Hombach, V., Marx, N. (2006). LXR Activation Reduces Proinflammatory Cytokine Expression in Human CD4-Positive Lymphocytes. Arterioscler. Thromb. Vasc. Bio. 26: 1022-1028 [Abstract] [Full Text]
Bochaton-Piallat, M.-L., Gabbiani, G. (2006). Smooth Muscle Cell: A Key Cell for Plaque Vulnerability Regulation?. Circ. Res. 98: 448-449 [Full Text]
Douglas, K M J, Pace, A V, Treharne, G J, Saratzis, A, Nightingale, P, Erb, N, Banks, M J, Kitas, G D (2006). Excess recurrent cardiac events in rheumatoid arthritis patients with acute coronary syndrome. Ann Rheum Dis 65: 348-353 [Abstract] [Full Text]
Hemdahl, A.-L., Gabrielsen, A., Zhu, C., Eriksson, P., Hedin, U., Kastrup, J., Thoren, P., Hansson, G. K. (2006). Expression of Neutrophil Gelatinase-Associated Lipocalin in Atherosclerosis and Myocardial Infarction. Arterioscler. Thromb. Vasc. Bio. 26: 136-142 [Abstract] [Full Text]
Dimayuga, P. C., Li, H., Chyu, K.-Y., Fredrikson, G. N., Nilsson, J., Fishbein, M. C., Shah, P. K., Cercek, B. (2005). T Cell Modulation of Intimal Thickening After Vascular Injury: The Bimodal Role of IFN-{gamma} in Immune Deficiency. Arterioscler. Thromb. Vasc. Bio. 25: 2528-2534 [Abstract] [Full Text]
van Beurden, H.E., Von den Hoff, J.W., Torensma, R., Maltha, J.C., Kuijpers-Jagtman, A.M. (2005). Myofibroblasts in Palatal Wound Healing: Prospects for the Reduction of Wound Contraction after Cleft Palate Repair. JDR 84: 871-880 [Abstract] [Full Text]
Hansson, G. K. (2005). Inflammation, Atherosclerosis, and Coronary Artery Disease. NEJM 352: 1685-1695 [Full Text]
Zhou, X., Robertson, A.-K. L., Rudling, M., Parini, P., Hansson, G. K. (2005). Lesion Development and Response to Immunization Reveal a Complex Role for CD4 in Atherosclerosis. Circ. Res. 96: 427-434 [Abstract] [Full Text]
Wang, S.-X., Elder, P. K., Zheng, Y., Strauch, A. R., Kelm, R. J. Jr. (2005). Cell Cycle-mediated Regulation of Smooth Muscle {alpha}-Actin Gene Transcription in Fibroblasts and Vascular Smooth Muscle Cells Involves Multiple Adenovirus E1A-interacting Cofactors. J. Biol. Chem. 280: 6204-6214 [Abstract] [Full Text]
Stocker, R., Keaney, J. F. Jr. (2004). Role of Oxidative Modifications in Atherosclerosis. Physiol. Rev. 84: 1381-1478 [Abstract] [Full Text]
Liu, X., Ostrom, R. S., Insel, P. A. (2004). cAMP-elevating agents and adenylyl cyclase overexpression promote an antifibrotic phenotype in pulmonary fibroblasts. Am. J. Physiol. Cell Physiol. 286: C1089-C1099 [Abstract] [Full Text]
Densem, C. G., Hutchinson, I. V., Yonan, N., Brooks, N. H. (2004). Influence of IFN-{gamma} polymorphism on the development of coronary vasculopathy after cardiac transplantation. Ann. Thorac. Surg. 77: 875-880 [Abstract] [Full Text]
Yamauchi, R., Tanaka, M., Kume, N., Minami, M., Kawamoto, T., Togi, K., Shimaoka, T., Takahashi, S., Yamaguchi, J., Nishina, T., Kitaichi, M., Komeda, M., Manabe, T., Yonehara, S., Kita, T. (2004). Upregulation of SR-PSOX/CXCL16 and Recruitment of CD8+ T Cells in Cardiac Valves During Inflammatory Valvular Heart Disease. Arterioscler. Thromb. Vasc. Bio. 24: 282-287 [Abstract] [Full Text]
Gojova, A., Brun, V., Esposito, B., Cottrez, F., Gourdy, P., Ardouin, P., Tedgui, A., Mallat, Z., Groux, H. (2003). Specific abrogation of transforming growth factor-{beta} signaling in T cells alters atherosclerotic lesion size and composition in mice. Blood 102: 4052-4058 [Abstract] [Full Text]
Kolodsick, J. E., Peters-Golden, M., Larios, J., Toews, G. B., Thannickal, V. J., Moore, B. B. (2003). Prostaglandin E2 Inhibits Fibroblast to Myofibroblast Transition via E. Prostanoid Receptor 2 Signaling and Cyclic Adenosine Monophosphate Elevation. Am. J. Respir. Cell Mol. Bio. 29: 537-544 [Abstract] [Full Text]
Elhage, R., Jawien, J., Rudling, M., Ljunggren, H.-G., Takeda, K., Akira, S., Bayard, F., Hansson, G. K (2003). Reduced atherosclerosis in interleukin-18 deficient apolipoprotein E-knockout mice. Cardiovasc Res 59: 234-240 [Abstract] [Full Text]
Hansson, G. K., Libby, P., Schonbeck, U., Yan, Z.-Q. (2002). Innate and Adaptive Immunity in the Pathogenesis of Atherosclerosis. Circ. Res. 91: 281-291 [Abstract] [Full Text]
Marx, N., Kehrle, B., Kohlhammer, K., Grub, M., Koenig, W., Hombach, V., Libby, P., Plutzky, J. (2002). PPAR Activators as Antiinflammatory Mediators in Human T Lymphocytes: Implications for Atherosclerosis and Transplantation-Associated Arteriosclerosis. Circ. Res. 90: 703-710 [Abstract] [Full Text]
Hughes, T. R., Tengku-Muhammad, T. S., Irvine, S. A., Ramji, D. P. (2002). A Novel Role of Sp1 and Sp3 in the Interferon-gamma -mediated Suppression of Macrophage Lipoprotein Lipase Gene Transcription. J. Biol. Chem. 277: 11097-11106 [Abstract] [Full Text]
Zhu, B., Reardon, C. A., Getz, G. S., Hui, D. Y. (2002). Both Apolipoprotein E and Immune Deficiency Exacerbate Neointimal Hyperplasia After Vascular Injury in Mice. Arterioscler. Thromb. Vasc. Bio. 22: 450-455 [Abstract] [Full Text]
Gerdes, N., Sukhova, G. K., Libby, P., Reynolds, R. S., Young, J. L., Schonbeck, U. (2002). Expression of Interleukin (IL)-18 and Functional IL-18 Receptor on Human Vascular Endothelial Cells, Smooth Muscle Cells, and Macrophages: Implications for Atherogenesis. JEM 195: 245-257 [Abstract] [Full Text]
Hansson, G. K. (2001). Immune Mechanisms in Atherosclerosis. Arterioscler. Thromb. Vasc. Bio. 21: 1876-1890 [Abstract] [Full Text]
Hansson, G.K. (2001). The stabilized plaque: will the dream come true?. Eur Heart J Suppl 3: C69-C75
Grewal, T., Priceputu, E., Davignon, J., Bernier, L. (2001). Identification of a {{gamma}}-Interferon-Responsive Element in the Promoter of the Human Macrophage Scavenger Receptor A Gene. Arterioscler. Thromb. Vasc. Bio. 21: 825-831 [Abstract] [Full Text]
Dorai, H., Sampath, T K. (2001). Bone Morphogenetic Protein-7 Modulates Genes that Maintain the Vascular Smooth Muscle Cell Phenotype in Culture. JBJS 83: S70-78 [Abstract] [Full Text]
Remskar, M., Li, H., Chyu, K.-Y., Shah, P. K., Cercek, B. (2001). Absence of CD40 Signaling Is Associated With an Increase in Intimal Thickening After Arterial Injury. Circ. Res. 88: 390-394 [Abstract] [Full Text]
Dorai, H., Sampath, T K. (2001). Bone Morphogenetic Protein-7 Modulates Genes that Maintain the Vascular Smooth Muscle Cell Phenotype in Culture. JBJS 83: S70-S78 [Abstract] [Full Text]
Kosaka, S., Takahashi, S., Masamura, K., Kanehara, H., Sakai, J., Tohda, G., Okada, E., Oida, K., Iwasaki, T., Hattori, H., Kodama, T., Yamamoto, T., Miyamori, I. (2001). Evidence of Macrophage Foam Cell Formation by Very Low-Density Lipoprotein Receptor : Interferon-{{gamma}} Inhibition of Very Low-Density Lipoprotein Receptor Expression and Foam Cell Formation in Macrophages. Circulation 103: 1142-1147 [Abstract] [Full Text]
Tegos, T. J., Kalodiki, E., Sabetai, M. M., Nicolaides, A. N. (2001). The Genesis of Atherosclerosis and Risk Factors: A Review. ANGIOLOGY 52: 89-98 [Abstract]
Waugh, J. M., Li-Hawkins, J., Yuksel, E., Kuo, M. D., Cifra, P. N., Hilfiker, P. R., Geske, R., Chawla, M., Thomas, J., Shenaq, S. M., Dake, M. D., Woo, S. L. C. (2000). Thrombomodulin Overexpression to Limit Neointima Formation. Circulation 102: 332-337 [Abstract] [Full Text]
Abberton, K.M., Healy, D.L., Rogers, P.A.W. (1999). Smooth muscle alpha actin and myosin heavy chain expression in the vascular smooth muscle cells surrounding human endometrial arterioles. Hum Reprod 14: 3095-3100 [Abstract] [Full Text]
Whitman, S. C., Argmann, C. A., Sawyez, C. G., Miller, D. B., Hegele, R. A., Huff, M. W. (1999). Uptake of type IV hypertriglyceridemic VLDL by cultured macrophages is enhanced by interferon-{gamma}. J. Lipid Res. 40: 1017-1028 [Abstract] [Full Text]
Newby, A. C, Zaltsman, A. B (1999). Fibrous cap formation or destruction -- the critical importance of vascular smooth muscle cell proliferation, migration and matrix formation. Cardiovasc Res 41: 345-360 [Abstract] [Full Text]
de Boer, O. J., van der Wal, A. C., Teeling, P., Becker, A. E. (1999). Leucocyte recruitment in rupture prone regions of lipid-rich plaques: a prominent role for neovascularization?. Cardiovasc Res 41: 443-449 [Abstract] [Full Text]
Presti, R. M., Pollock, J. L., Dal Canto, A. J., O'Guin, A. K., Virgin, H. W. IV (1998). Interferon {gamma} Regulates Acute and Latent Murine Cytomegalovirus Infection and Chronic Disease of the Great Vessels. JEM 188: 577-588 [Abstract] [Full Text]
Gabbiani, G. (1998). Evolution and clinical implications of the myofibroblast concept. Cardiovasc Res 38: 545-548 [Full Text]
Matthys, K. E., Van Hove, C. E., Kockx, M. M., Andries, L. J., Van Osselaer, N., Herman, A. G., Bult, H. (1997). Local Application of LDL Promotes Intimal Thickening in the Collared Carotid Artery of the Rabbit. Arterioscler. Thromb. Vasc. Bio. 17: 2423-2429 [Abstract] [Full Text]
Geng, Y.-J., Henderson, L. E., Levesque, E. B., Muszynski, M., Libby, P. (1997). Fas Is Expressed in Human Atherosclerotic Intima and Promotes Apoptosis of Cytokine-Primed Human Vascular Smooth Muscle Cells. Arterioscler. Thromb. Vasc. Bio. 17: 2200-2208 [Abstract] [Full Text]
Kockx, M. M., De Meyer, G. R.Y., Bortier, H., de Meyere, N., Muhring, J., Bakker, A., Jacob, W., Van Vaeck, L., Herman, A. (1996). Luminal Foam Cell Accumulation Is Associated With Smooth Muscle Cell Death in the Intimal Thickening of Human Saphenous Vein Grafts. Circulation 94: 1255-1262 [Abstract] [Full Text]
Geng, Y.-J., Wu, Q., Muszynski, M., Hansson, G. K., Libby, P. (1996). Apoptosis of Vascular Smooth Muscle Cells Induced by In Vitro Stimulation With Interferon-{gamma}, Tumor Necrosis Factor�{alpha}, and Interleukin-1�. Arterioscler. Thromb. Vasc. Bio. 16: 19-27 [Abstract] [Full Text]
Geng, Y.-j., Holm, J., Nygren, S., Bruzelius, M., Stemme, S., Hansson, G. K. (1995). Expression of the Macrophage Scavenger Receptor in Atheroma : Relationship to Immune Activation and the T-Cell Cytokine Interferon-{gamma}. Arterioscler. Thromb. Vasc. Bio. 15: 1995-2002 [Abstract] [Full Text]
Schwartz, S. M., deBlois, D., O'Brien, E. R. M. (1995). The Intima : Soil for Atherosclerosis and Restenosis. Circ. Res. 77: 445-465 [Full Text]
Rolfe, B. E., Campbell, J. H., Smith, N. J., Cheong, M. W., Campbell, G. R. (1995). T Lymphocytes Affect Smooth Muscle Cell Phenotype and Proliferation. Arterioscler. Thromb. Vasc. Bio. 15: 1204-1210 [Abstract] [Full Text]
Villa, A. E., Guzman, L. A., Poptic, E. J., Labhasetwar, V., D'Souza, S., Farrell, C. L., Plow, E. F., Levy, R. J., DiCorleto, P. E., Topol, E. J. (1995). Effects of Antisense c-myb Oligonucleotides on Vascular Smooth Muscle Cell Proliferation and Response to Vessel Wall Injury. Circ. Res. 76: 505-513 [Abstract] [Full Text]
Marx, N., Kehrle, B., Kohlhammer, K., Grub, M., Koenig, W., Hombach, V., Libby, P., Plutzky, J. (2002). PPAR Activators as Antiinflammatory Mediators in Human T Lymphocytes: Implications for Atherosclerosis and Transplantation-Associated Arteriosclerosis. Circ. Res. 90: 703-710 [Abstract] [Full Text]