Interleukin-10 attenuates vascular responses to endothelin-1 via effects on ERK1/2-dependent pathway

Author(s)

Giachini, Fernanda R. C. ^{[1, 2]} ; Zemse, Saiprasad M. ^[2] ; Carneiro, Fernando S. ^{[1, 2]} ; Lima, Victor V. ^[2] ; Carneiro, Zidonia N. ^[2] ; Callera, Glaucia E. ^[3] ; Ergul, Adviye ^[2] ; Webb, R. Clinton ^[2] ; Tostes, Rita C. ^{[1, 2]}

Affiliation

^[1] Univ Sao Paulo, Dept Pharmacol, Sao Paulo - Brazil

^[2] Med Coll Georgia, Dept Physiol, Augusta, GA 30912 - USA

^[3] Univ Ottawa, Kidney Res Ctr, Ottawa, ON - Canada

• Document type: Journal article
• Source: AMERICAN JOURNAL OF PHYSIOLOGY-HEART AND CIRCULATORY PHYSIOLOGY; v. 296, n. 2, p. H489-H496, FEB 2009.
• Web of Science Citations: 17

Abstract

Giachini FR, Zemse SM, Carneiro FS, Lima VV, Carneiro ZN, Callera GE, Ergul A, Webb RC, Tostes RC. Interleukin-10 attenuates vascular responses to endothelin-1 via effects on ERK1/2-dependent pathway. Am J Physiol Heart Circ Physiol 296: H489-H496, 2009. First published December 12, 2008; doi:10.1152/ajpheart.00251.2008.-Interleukin-10 (IL-10) is an anti-inflammatory cytokine with protective actions on the vasculature. On the other hand, endothelin ( ET)-1 has potent vasoconstrictor, mitogenic, and proinflammatory activities, which have been implicated in the pathophysiology of a number of cardiovascular diseases. We hypothesized that, in a condition where ET-1 expression is upregulated, i.e., on infusion of TNF-alpha, IL-10 confers vascular protection from ET-1-induced injury. Aortic rings and first-order mesenteric arteries from male C57BL/6 (WT) and IL-10-knockout (IL-10(-/-)) mice were treated with human recombinant TNF-alpha (220 ng.kg(-1).day(-1)) or vehicle (saline) for 14 days. TNF-alpha infusion significantly increased blood pressure in IL-10(-/-), but not WT, mice. TNF-alpha augmented vascular ET-1 mRNA expression in arteries from WT and IL-10(-/-) mice. ET type A (ETA) receptor expression was increased in arteries from IL-10(-/-) mice, and TNF-alpha infusion did not change vascular ETA receptor expression in control or IL-10(-/-) mice. Aorta and mesenteric arteries from TNF-alpha-infused IL-10(-/-) mice displayed increased contractile responses to ET-1, but not the ET type B receptor agonist IRL-1620. The ETA receptor antagonist atrasentan completely abolished responses to ET-1 in aorta and mesenteric vessels, whereas the ERK1/2 inhibitor PD-98059 abrogated increased contractions to ET-1 in arteries from TNF-alpha-infused IL-10(-/-) mice. Infusion of TNF-alpha, as well as knockdown of IL-10 (IL-10(-/-)), induced an increase in total and phosphorylated ERK1/2. These data demonstrate that IL-10 counteracts ET(A)-mediated vascular responses to ET-1, as well as activation of the ERK1/2 pathway. (AU)

• FAPESP's process: 06/01773-0 - RhoA/Rho-cinase signaling pathway in the vascular smooth muscle from mice with angiotensin II-induced hypertension: interaction with reactive oxygen species, interleukin-6 (IL-6) and JAK/STAT activation
• Grantee: Rita de Cassia Aleixo Tostes Passaglia
• Support Opportunities: Scholarships abroad - New Frontiers