Abstract
Chemokines promote vascular inflammation and play a pathogenic role in the development and maintenance of hypertension. In the present study, the expression of the chemokine interleukin-8/CXCL8 (IL-8/CXCL8) was investigated in cultured vascular smooth muscle cells (VSMC) obtained from the thoracic aorta of spontaneously hypertensive rats (SHR) and normotensive Wistar-Kyoto rats (WKY). IL-8/CXCL8 expression in thoracic aorta tissue and VSMC in SHR were significantly higher than in WKY. However, the expression of CXCR1 mRNA in VSMC from WKY was higher than that in VSMC from SHR. Angiotensin II (Ang II) induced a higher level of IL-8/CXCL8 mRNA expression in VSMC from SHR than in VSMC from WKY. The time course of Ang II–induced IL-8/CXCL8 expression in VSMC from SHR correlated with those of Ang II–induced CXCL1 and Ang II type 1 (AT1) receptor expression, and the expression of IL-8/CXCL8 by Ang II was inhibited by the AT1 receptor antagonist losartan. The effect of Ang II on IL-8/CXCL8 expression was not dependent on nuclear factor-κB (NF-κB) activation, but was mediated by an extracellular signal–regulated kinase (ERK) signaling pathway. Although Ang II directly induced IL-8/CXCL8 expression, expression of Ang II–induced IL-8/CXCL8 decreased in VSMC transfected with heme oxygenase-1. These results suggest that IL-8/CXCL8 plays an important role in the pathogenesis of Ang II–induced hypertension and vascular lesions in SHR.
Similar content being viewed by others
Article PDF
References
Alexander RW : Hypertension and the pathogenesis of atherosclerosis. Hypertension 1995; 25: 155–161.
Gerszten RE : Pleiotropic effects of chemokines in vascular lesion development. Artherioscler Thromb Vasc Biol 2002; 22: 528–529.
Luster AD : Chemokines—chemotactic cytokines that mediate inflammation. N Engl J Med 1998; 338: 436–445.
Spinetti G, Wang M, Monticone R, Zhang J, Zhao D, Lakatta EG : Rat aortic MCP-1 and its receptor CCR2 increase with age and alter vascular smooth muscle cell function. Arterioscler Thromb Vasc Biol 2004; 24: 1397–1402.
Ishibashi M, Hiasa KI, Zhao Q, et al: Critical role of monocyte chemoattractant protein-1 receptor CCR2 on monocyte in hypertension-induced vascular inflammation and remodeling. Circ Res 2004; 94: 1203–1210.
Capers QI, Alexander RW, Lou P, et al: Monocyte chemoattractant protein-1 expression in aortic tissues of hypertensive rats. Hypertension 1997; 30: 1397–1402.
Parissis JT, Korovesis S, Giazitzoglou E, Kalivas P, Katritsis D : Plasma profile of peripheral monocyte-related inflammatory markers in patients with arterial hypertension. Correlations with plasma endothelin-1. Int J Cardiol 2002; 83: 13–21.
Zhang Y, Griendling KK, Dikalova A, Owens GK, Talyor WR : Vascular hypertrophy in angiotensin II–induced hypertension is mediated by vascular smooth muscle cell–derived H2O2 . Hypertension 2005; 46: 732–737.
Rodríguez-Iturbe B, Vaziri ND, Herrera-Acosta J, Johnson RJ : Oxidative stress, renal infiltration of immune cells and salt-sensitive hypertension: all for one and one for all. Am J Physiol 2004; 286: F606–F616.
Chen XL, Tummala PE, Olbrych MT, Alexander RW, Medford RM : Angiotensin II induces monocyte chemoattractant protein-1 gene expression in rat vascular smooth muscle cells. Circ Res 1998; 83: 952–959.
Xie QY, Sun M, Yang TL, Sun ZL : Losartan reduces monocyte chemoattractant protein-1 expression in aortic tissues of 2K1C hypertensive rats. Int J Cardiol 2006; 110: 60–66.
Gerszten RE, Garcia-Zepeda EA, Lim YC, et al: MCP-1 and IL-8 trigger firm adhesion of monocytes to vascular endothelium under flow conditions. Nature 1999; 398: 718–723.
Griendling KK, Taubman MB, Akers M, Mendlowitz M, Alexander RW : Characterization of phosphatidylinositol-specific phospholipase C from cultured vascular smooth muscle cells. J Biol Chem 1991; 266: 15498–15504.
Kim HY, Kim HK, Kim JR, Kim HS : Upregulation of LPS-induced chemokine KC expression by 15-deoxy-Δ12,14-prostagladin J2 in mouse peritoneal macrophages. Immunol Cell Biol 2005; 83: 286–293.
Thomson AW, Lotze MT ( eds): The Cytokine Handbook. Academic Press, 4th ed. San Diego, Elsevier Science, 2003, pp 1056–1057.
Boekholdt S, Peters R, Hack CE, et al: IL-8 plasma concentrations and the risk of future coronary artery disease in apparently healthy men and women. Arterioscler Thromb Vasc Biol 2004; 24: 1503–1508.
Buemi M, Marino D, Floccari F, et al: Effect of interleukin 8 and ICAM-1 on calcium-dependent outflow of K+ in erythrocytes from subjects with essential hypertension. Curr Med Res Opin 2004; 20: 19–24.
Rodriguez-Iturbe B, Ferrebuz A, Vanegas V, Quiroz Y, Mezzano S, Vaziri ND : Early and sustained inhibition of nuclear factor-κB prevents hypertension in spontaneously hypertensive rats. J Pharmacol Exp Ther 2005; 315: 51–57.
Arndt H, Smith CW, Granger N : Leukocyte-endothelial cell adhesion in spontaneously hypertensive and normotensive rats. Hypertension 1993; 21: 667–673.
Rajagopalan S, Kurz S, Munzel T, et al: Angiotensin II mediated hypertension in the rat increase vascular superoxide production via membrane NADH/NADPH oxidase activation: contribution to alterations of vasomotor tone. J Clin Invest 1996; 97: 1916–1923.
Griendling KK, Minieri CA, Ollerenshaw JD, Alexander RW : Angiotensin II stimulates NADH oxidase activity in cultured vascular smooth muscle cells. Circ Res 1994; 74: 1141–1148.
Wolf G, Ziyadeh FN, Thaiss F, et al: Angiotensin II stimulates expression of the chemokine RANTES in rat glomerular endothelial cells. Role of the angiotensin type 2 receptor. J Clin Invest 1997; 100: 1047–1058.
Zahradka P, Werner JP, Buhay S, Litchie B, Helwer G, Thomas S : NF-κB activation is essential for angiotensin II–dependent proliferation and migration of vascular smooth muscle cells. J Mol Cell Cardiol 2002; 34: 1609–1621.
Kranzhofer R, Schmidt J, Preiffer CA, Hagl S, Libby P, Kubler W : Angiotensin induces inflammatory activation of human vascular smooth muscle cells. Arterioscler Thromb Vasc Biol 1999; 19: 1623–1629.
Wolf G, Wenzel U, Burns KD, Harris RC, Stahl RAK, Thaiss F : Angiotensin II activates nuclear transcription factor-κB through AT1 and AT2 receptors. Kidney Int 2002; 61: 1986–1995.
Ruiz-Ortega M, Lorenzo O, Ruperez M, et al: Angiotensin II activates nuclear transcription factor κB trough AT1 and AT2 in vascular smooth muscle cells. Circ Res 2000; 86: 1266–1272.
Duff JL, Berk BC, Corson MA : Angiotensin II stimulate the pp44 and pp42 mitogen-activated protein kinase in cultured rat aortic smooth muscle cells. Biochem Biophys Res Commun 1992; 188: 257–264.
Duff JL, Minia BP, Berk BC : Mitogen-activated protein (MAP) kinase is regulated by the MAP kinase phosphatase (MKP-1) in vascular smooth muscle cells: effect of actinomycin D and antisense oligonucleotides. J Biol Chem 1995; 270: 7161–7166.
Botros FT, Schwartzman ML, Stier CT Jr, Goodman AI, Abraham NG : Increase in heme oxygenase-1 levels ameliorates renovascular hypertension. Kidney Int 2005; 68: 2745–2755.
Sabaawy HE, Zhang F, Nguyen X, et al: Human heme oxygenase-1 gene transfer lowers blood pressure and promotes growth in spontaneously hypertensive rats. Hypertension 2001; 38: 210–215.
Yang L, Quan S, Nasjletti A, Laniado-Schwartzman M, Abraham NG : Heme oxygenase-1 gene expression modulates angiotensin II–induced increase in blood pressure. Hypertension 2004; 43: 1221–1226.
Vera T, Kelsen S, Yanes LL, Reckelhoff JF, Stec DE : HO-1 induction lowers blood pressure and superoxide production in the renal medulla of angiotensin II hypertensive mice. Am J Physiol Regul Integr Comp Physiol 2007; 292: R1472–R1478.
Quan S, Yang L, Shnouda S, et al: Expression of human heme oxygenase-1 in the thick ascending limb attenuates angiotensin II–mediated increase in oxidative injury. Kidney Int 2004; 65: 1628–1639.
Park HS, Chun JN, Jung HY, Choi C, Bae YS : Role of NADPH oxidase 4 in lipopolysaccharide-induced proinflammatory responses by human aortic endothelial cells. Cardiovasc Res 2006; 72: 447–455.
Nakanaga T, Nadel JA, Ueki IF, Koff JL, Shao MX : Regulation of interleukin-8 via an airway epithelial signaling cascade. Am J Physiol Lung Cell Mol Physiol 2007; 292: L1289–L1296.
Author information
Authors and Affiliations
Corresponding author
Rights and permissions
About this article
Cite this article
Kim, H., Kang, Y., Song, I. et al. Upregulation of Interleukin-8/CXCL8 in Vascular Smooth Muscle Cells from Spontaneously Hypertensive Rats. Hypertens Res 31, 515–523 (2008). https://doi.org/10.1291/hypres.31.515
Received:
Accepted:
Issue date:
DOI: https://doi.org/10.1291/hypres.31.515
Keywords
This article is cited by
-
Immune cells and hypertension
Immunologic Research (2024)
-
Pro-inflammatory cytokines of rat vasculature in DOCA-salt treatment
Molecular Biology Reports (2010)
