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

Fernanda R.C. Giachini, Saiprasad M. Zemse, Fernando S. Carneiro, Victor V. Lima, Zidonia N. Carneiro, Glaucia E. Callera, Adviye Ergul, R Clinton Webb, Rita C. Tostes

Research output: Contribution to journalArticle

18 Citations (Scopus)

Abstract

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-α, 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-α (220 ng• kg -1 • day -1) or vehicle (saline) for 14 days. TNF-α infusion significantly increased blood pressure in IL-10 -/-, but not WT, mice. TNF-α augmented vascular ET-1 mRNA expression in arteries from WT and IL-10 -/- mice. ET type A (ET A) receptor expression was increased in arteries from IL-10 -/- mice, and TNF-α infusion did not change vascular ETA receptor expression in control or IL-10 -/- mice. Aorta and mesenteric arteries from TNF-α-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-α-infused IL-10 -/- mice. Infusion of TNF-α, as well as knockdown of IL-10 (IL-10 -/-), induced an increase in total and phosphor- ylated ERK1/2. These data demonstrate that IL-10 counteracts ETA- mediated vascular responses to ET-1, as well as activation of the ERK1/2 pathway.

Original languageEnglish (US)
JournalAmerican Journal of Physiology - Heart and Circulatory Physiology
Volume296
Issue number2
DOIs
StatePublished - Feb 1 2009

Fingerprint

MAP Kinase Signaling System
Endothelin-1
Interleukin-10
Blood Vessels
Mesenteric Arteries
Arteries
Aorta
Endothelin B Receptors
Endothelin A Receptors
Vasoconstrictor Agents
Knockout Mice
Anti-Inflammatory Agents
Cardiovascular Diseases

Keywords

  • Blood pressure
  • Tumor necrosis factor-α
  • Vascular reactivity

ASJC Scopus subject areas

  • Physiology
  • Cardiology and Cardiovascular Medicine
  • Physiology (medical)

Cite this

Interleukin-10 attenuates vascular responses to endothelin-1 via effects on ERK1/2-dependent pathway. / Giachini, Fernanda R.C.; Zemse, Saiprasad M.; Carneiro, Fernando S.; Lima, Victor V.; Carneiro, Zidonia N.; Callera, Glaucia E.; Ergul, Adviye; Webb, R Clinton; Tostes, Rita C.

In: American Journal of Physiology - Heart and Circulatory Physiology, Vol. 296, No. 2, 01.02.2009.

Research output: Contribution to journalArticle

Giachini, Fernanda R.C. ; Zemse, Saiprasad M. ; Carneiro, Fernando S. ; Lima, Victor V. ; Carneiro, Zidonia N. ; Callera, Glaucia E. ; Ergul, Adviye ; Webb, R Clinton ; Tostes, Rita C. / Interleukin-10 attenuates vascular responses to endothelin-1 via effects on ERK1/2-dependent pathway. In: American Journal of Physiology - Heart and Circulatory Physiology. 2009 ; Vol. 296, No. 2.
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AU - Lima, Victor V.

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