TY - JOUR
T1 - Interleukin-10 negatively modulates extracellular signal-regulated kinases 1 and 2 in aorta from hypertensive mouse induced by angiotensin II infusion
AU - Bressan, Alecsander F.
AU - Fonseca, Gisele A.
AU - Tostes, Rita C.
AU - Webb, R Clinton
AU - Lima, Victor Vitorino
AU - Giachini, Fernanda Regina
N1 - Funding Information:
This work was supported in part by grants from L’Oréal—For Women in Sciences—Edition 2013—Brazil (to F.R.G), Funda©cão de Amparo à Pesquisa do Estado de Mato Grosso (FAPEMAT) [grant number 151371/2014 (to F.R.G.], Coordena©cão de Aperfeic©oa-mento de Pessoal de Ńıvel Superior (CAPES) [grant number 23038009165/2013-48 (to V.V.L.], Funda©cão de Amparo à Pesquisa do Estado de São Paulo (FAPESP) [grant number 2010/52214-6 (to R.C.T)], Conselho Nacional de Desenvolvimento Científico e Tecnológico [(CNPq) 471675/2013-0 (to F.R.G.], and National Institutes of Health (NIH) [HL134604 and DK83685 (R.C.W)]. The agencies had no role in study design, data collection, and analysis, decision to publish, or preparation of the manuscript. We would also like to thank all the technical staff, who have worked in our laboratories and contributed to the studies described here.
Funding Information:
This work was supported in part by grants from L'Or?al?For Women in Sciences?Edition 2013?Brazil (to F.R.G), Funda??o de Amparo ? Pesquisa do Estado de Mato Grosso (FAPEMAT) [grant number 151371/2014 (to F.R.G.], Coordena??o de Aperfei?oamento de Pessoal de N?vel Superior (CAPES) [grant number 23038009165/2013-48 (to V.V.L.], Funda??o de Amparo ? Pesquisa do Estado de S?o Paulo (FAPESP) [grant number 2010/52214-6 (to R.C.T)], Conselho Nacional de Desenvolvimento Cient?fico e Tecnol?gico [(CNPq) 471675/2013-0 (to F.R.G.], and National Institutes of Health (NIH) [HL134604 and DK83685 (R.C.W)]. The agencies had no role in study design, data collection, and analysis, decision to publish, or preparation of the manuscript. We would also like to thank all the technical staff, who have worked in our laboratories and contributed to the studies described here.
Publisher Copyright:
© 2018 Société Française de Pharmacologie et de Thérapeutique
PY - 2019/2
Y1 - 2019/2
N2 - The activation of extracellular signal-regulated kinase 1 and 2 (ERK 1/2) pathway promotes increased vascular contractility in angiotensin II (Ang II)-induced hypertensive mice. Interleukin-10 (IL-10) is an immune-regulatory cytokine with the ability to prevent vascular hypercontractility during hypertension. We hypothesized that IL-10 would downregulate vascular ERK 1/2 activation during Ang II-induced hypertension. Wild-type (WT) or IL-10 knockout (IL-10−/−) mice received Ang II infusion (90 ηg.min) or vehicle (saline), via osmotic mini-pumps (0.25 μL/h for 14 days), whereas another WT group were infused with exogenous IL-10 (0.5 ηg/min, 14 days) simultaneously, or not, with Ang II. Aortic rings were mounted in a myograph, and concentration-response curves to phenylephrine were evaluated, in the presence or absence of ERK 1/2 inhibitor (PD98059, 10 μm, 40 min). Protein expression of vascular ERK 1/2 was determined by Western blot. Ang II infusion increased the maximal contractile response in both WT and IL-10−/− mice. Concomitant infusion of IL-10 and Ang II prevented hypercontractility in the vasculature. Exogenous IL-10 infusion prevented ERK 1/2 activation and hypercontractility, induced by Ang II. These findings suggest that IL-10 negatively modulates ERK 1/2 activation and prevents hypercontractility during Ang II-induced hypertension.
AB - The activation of extracellular signal-regulated kinase 1 and 2 (ERK 1/2) pathway promotes increased vascular contractility in angiotensin II (Ang II)-induced hypertensive mice. Interleukin-10 (IL-10) is an immune-regulatory cytokine with the ability to prevent vascular hypercontractility during hypertension. We hypothesized that IL-10 would downregulate vascular ERK 1/2 activation during Ang II-induced hypertension. Wild-type (WT) or IL-10 knockout (IL-10−/−) mice received Ang II infusion (90 ηg.min) or vehicle (saline), via osmotic mini-pumps (0.25 μL/h for 14 days), whereas another WT group were infused with exogenous IL-10 (0.5 ηg/min, 14 days) simultaneously, or not, with Ang II. Aortic rings were mounted in a myograph, and concentration-response curves to phenylephrine were evaluated, in the presence or absence of ERK 1/2 inhibitor (PD98059, 10 μm, 40 min). Protein expression of vascular ERK 1/2 was determined by Western blot. Ang II infusion increased the maximal contractile response in both WT and IL-10−/− mice. Concomitant infusion of IL-10 and Ang II prevented hypercontractility in the vasculature. Exogenous IL-10 infusion prevented ERK 1/2 activation and hypercontractility, induced by Ang II. These findings suggest that IL-10 negatively modulates ERK 1/2 activation and prevents hypercontractility during Ang II-induced hypertension.
KW - MAP kinase
KW - cytokine
KW - smooth muscle cell and contraction
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U2 - 10.1111/fcp.12409
DO - 10.1111/fcp.12409
M3 - Article
C2 - 30144156
AN - SCOPUS:85052944651
SN - 0767-3981
VL - 33
SP - 31
EP - 40
JO - Fundamental and Clinical Pharmacology
JF - Fundamental and Clinical Pharmacology
IS - 1
ER -