TY - JOUR
T1 - Interleukin-10 attenuates vascular responses to endothelin-1 via effects on ERK1/2-dependent pathway
AU - Giachini, Fernanda R.C.
AU - Zemse, Saiprasad M.
AU - Carneiro, Fernando S.
AU - Lima, Victor V.
AU - Carneiro, Zidonia N.
AU - Callera, Glaucia E.
AU - Ergul, Adviye
AU - Webb, R. Clinton
AU - Tostes, Rita C.
PY - 2009/2
Y1 - 2009/2
N2 - 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.
AB - 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.
KW - Blood pressure
KW - Tumor necrosis factor-α
KW - Vascular reactivity
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U2 - 10.1152/ajpheart.00251.2008
DO - 10.1152/ajpheart.00251.2008
M3 - Article
C2 - 19074677
AN - SCOPUS:61949143689
SN - 0363-6135
VL - 296
SP - H489-H496
JO - American Journal of Physiology - Heart and Circulatory Physiology
JF - American Journal of Physiology - Heart and Circulatory Physiology
IS - 2
ER -