Abstract
Inappropriate vascular remodeling is thought to be the main cause of restenosis following angioplasty. Migration of vascular smooth muscle cells (VSMC) into lumina, which is promoted by degradation of the extracellular matrix by matrix metalloproteinases (MMPs) plays a causal role in pathological vascular remodeling. The aim of the present research is to explore the effects of a novel cytokine, IL-17, on migration of VSMC and MMP-9 secretion. Carotid artery VSMC was isolated from Sprague–Dawley rats. Expression of MMP-9 and cell migration induced by IL-17 and its related signal pathway were detected. The results showed that IL-17-induced migration of VSMC in an MMP-9-dependent manner. IL-17-induced MMP-9 expression was via p38 MAPK and ERK1/2 dependent NF-κB and AP-1 activation. The present results demonstrated that IL-17 may play a role in vascular remodeling and targeting IL-17 or its specific downstream mediators is a potentially novel therapeutic pathway for attenuating the post-angioplastic restenosis.
Similar content being viewed by others
References
Bettelli E, Oukka M, Kuchroo VK (2007) T(H)-17 cells in the circle of immunity and autoimmunity. Nat Immunol 8:345–350. doi:10.1038/ni0407-345
Chandrasekar B, Mummidi S, Mahimainathan L, Patel DN, Bailey SR, Imam SZ, Greene WC, Valente AJ (2006) Interleukin-18-induced human coronary artery smooth muscle cell migration is dependent on NF-kappaB- and AP-1-mediated matrix metalloproteinase-9 expression and is inhibited by atorvastatin. J Biol Chem 281:15099–15109. doi:10.1074/jbc.M600200200
Cho A, Reidy MA (2002) Matrix metalloproteinase-9 is necessary for the regulation of smooth muscle cell replication and migration after arterial injury. Circ Res 91:845–851. doi:10.1161/01.RES.0000040420.17366.2E
Cortez DM, Feldman MD, Mummidi S, Valente AJ, Steffensen B, Vincenti M, Barnes JL, Chandrasekar B (2007) IL-17 stimulates MMP-1 expression in primary human cardiac fibroblasts via p38 MAPK- and ERK1/2-dependent C/EBP-beta, NF-kappaB, and AP-1 activation. Am J Physiol Heart Circ Physiol 293:H3356–H3365. doi:10.1152/ajpheart.00928.2007
Eberhardt W, Huwiler A, Beck KF, Walpen S, Pfeilschifter J (2000) Amplification of IL-1 beta-induced matrix metalloproteinase-9 expression by superoxide in rat glomerular mesangial cells is mediated by increased activities of NF-kappa B and activating protein-1 and involves activation of the mitogen-activated protein kinase pathways. J Immunol 165:5788–5797
Galis ZS, Khatri JJ (2002) Matrix metalloproteinases in vascular remodeling and atherogenesis: the good, the bad, and the ugly. Circ Res 90:251–262
Galis ZS, Johnson C, Godin D, Magid R, Shipley JM, Senior RM, Ivan E (2002) Targeted disruption of the matrix metalloproteinase-9 gene impairs smooth muscle cell migration and geometrical arterial remodeling. Circ Res 91:852–859. doi:10.1161/01.RES.0000041036.86977.14
Gibbons GH, Dzau VJ (1994) The emerging concept of vascular remodeling. N Engl J Med 330:1431–1438. doi:10.1056/NEJM199405193302008
Hashmi S, Zeng QT (2006) Role of interleukin-17 and interleukin-17-induced cytokines interleukin-6 and interleukin-8 in unstable coronary artery disease. Coron Artery Dis 17:699–706. doi:10.1097/01.mca.0000236288.94553.b4
Ikeda U, Shimada K (2003) Matrix metalloproteinases and coronary artery diseases. Clin Cardiol 26:55–59. doi:10.1002/clc.4960260203
Liang KC, Lee CW, Lin WN, Lin CC, Wu CB, Luo SF, Yang CM (2007) Interleukin-1beta induces MMP-9 expression via p42/p44 MAPK, p38 MAPK, JNK, and nuclear factor-kappaB signaling pathways in human tracheal smooth muscle cells. J Cell Physiol 211:759–770. doi:10.1002/jcp.20992
Mnjoyan ZH, Doan D, Brandon JL, Felix K, Sitter CL, Rege AA, Brock TA, Fujise K (2008) The critical role of the intrinsic VSMC proliferation and death programs in injury-induced neointimal hyperplasia. Am J Physiol Heart Circ Physiol 294:H2276–H2284. doi:10.1152/ajpheart.91527.2007
Moon SK, Cha BY, Kim CH (2004) ERK1/2 mediates TNF-alpha-induced matrix metalloproteinase-9 expression in human vascular smooth muscle cells via the regulation of NF-kappaB and AP-1: Involvement of the ras dependent pathway. J Cell Physiol 198:417–427. doi:10.1002/jcp.10435
Moseley TA, Haudenschild DR, Rose L, Reddi AH (2003) Interleukin-17 family and IL-17 receptors. Cytokine Growth Factor Rev 14:155–174. doi:10.1016/S1359-6101(03)00002-9
Patel DN, King CA, Bailey SR, Holt JW, Venkatachalam K, Agrawal A, Valente AJ, Chandrasekar B (2007) Interleukin-17 stimulates C-reactive protein expression in hepatocytes and smooth muscle cells via p38 MAPK and ERK1/2-dependent NF-kappaB and C/EBPbeta activation. J Biol Chem 282:27229–27238. doi:10.1074/jbc.M703250200
Rahman MS, Yamasaki A, Yang J, Shan L, Halayko AJ, Gounni AS (2006) IL-17A induces eotaxin-1/CC chemokine ligand 11 expression in human airway smooth muscle cells: role of MAPK (Erk1/2, JNK, and p38) pathways. J Immunol 177:4064–4071
Ross R (1999a) Atherosclerosis is an inflammatory disease. Am Heart J 138:S419–S420. doi:10.1016/S0002-8703(99)70266-8
Ross R (1999b) Atherosclerosis–an inflammatory disease. N Engl J Med 340:115–126. doi:10.1056/NEJM199901143400207
Schwartz SM (1997) Perspectives series: cell adhesion in vascular biology. Smooth muscle migration in atherosclerosis and restenosis. J Clin Invest 99:2814–2816. doi:10.1172/JCI119472
Shen F, Hu Z, Goswami J, Gaffen SL (2006) Identification of common transcriptional regulatory elements in interleukin-17 target genes. J Biol Chem 281:24138–24148. doi:10.1074/jbc.M604597200
Yao Z, Fanslow WC, Seldin MF, Rousseau AM, Painter SL, Comeau MR, Cohen JI, Spriggs MK (1995) Herpesvirus Saimiri encodes a new cytokine, IL-17, which binds to a novel cytokine receptor. Immunity 3:811–821. doi:10.1016/1074-7613(95)90070-5
Yao JS, Zhai W, Fan Y, Lawton MT, Barbaro NM, Young WL, Yang GY (2007) Interleukin-6 upregulates expression of KDR and stimulates proliferation of human cerebrovascular smooth muscle cells. J Cereb Blood Flow Metab 27:510–520. doi:10.1038/sj.jcbfm.9600365
Acknowledgments
We would like to express our appreciations to Sun Zhidan for his excellent technical assistance and Li Wen for her revision of the draft. This research was sponsored partly by the Heilongjiang Youth Fund (QC07C100) and Special Fund of The First Affiliated Hospital of Harbin Medical University (2007035).
Author information
Authors and Affiliations
Corresponding author
Additional information
G. Cheng and L. Wei have contributed equally.
Rights and permissions
About this article
Cite this article
Cheng, G., Wei, L., Xiurong, W. et al. IL-17 Stimulates Migration of Carotid Artery Vascular Smooth Muscle Cells in an MMP-9 Dependent Manner via p38 MAPK and ERK1/2-Dependent NF-κB and AP-1 Activation. Cell Mol Neurobiol 29, 1161–1168 (2009). https://doi.org/10.1007/s10571-009-9409-z
Received:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1007/s10571-009-9409-z