Efeito modulador da angiotensina- (1-7) na via de sinalização da interleucina-10 : foco na vasculatura

• Autor(a) principal: Freitas, Raiany Alves de
• Data de Publicação: 2020
• Tipo de documento: Dissertação
• Idioma: por
• Título da fonte: Repositório Institucional da UFMT
• Texto Completo: http://ri.ufmt.br/handle/1/5044
• topic: Ang-(1-7); Sistema renina-angiotensina; Citocinas; MKP-1; CNPQ::CIENCIAS BIOLOGICAS::IMUNOLOGIA; Ang-(1-7); Renin-angiotensin system; Citokines; MKP-1

Angiotensin-1-7 [Ang-(1-7)] is an important peptide of the renin-angiotensin system capable of producing modulating, anti-inflammatory and vasodilatory effects, demonstrating recently to be able to activate mitogen-activated protein kinase phosphatase-1 (MKP-1), an important antagonist of the deleterious effects triggered by angiotensin II. Like Ang-(1-7), interleukin-10 (IL-10), a potentially anti-inflammatory and immunomodulatory cytokine, is characterized as an important regulator of MKP-1 in the vasculature. Although Ang-(1-7) and IL-10 have similar effects in vascular aspects, the association between these two mediators is still unknown. The aim of this study was to evaluate the modulating effect of Ang-(1-7) on the IL-10 signaling pathway and the consequence of this association in the expression/activity of MKP-1 and in the vascular contraction response. Male mice of the C57BL/6J [wild, (WT)] line and knockout for IL-10 [B6.12P2-Il10tm1Cgn/J (IL-10-/- )] were used at 8-12 weeks of age. Aortic artery segments were used to analyze vascular function through the concentration curve response to phenylephrine (0,1 nM to 100 μM). The other aortic segments were incubated with Ang-(1-7) [10 μM] or vehicle (H2O), for 5 min, 1 h, 6 h, 12 h and 24 h. After incubations, flow cytometry analyzes were performed, to measure tissue IL-10 levels, and Western Blot to quantify the tissue expression of JAK1, STAT3 and MKP-1. The experimental methodology was approved by the ethics committee on the use of animals number 014/2019. The results of the vascular function demonstrated that Ang-(1-7) reduces the vascular contraction induced by phenylephrine in the times of 5 min (7,45 ± 0,55 vs. 6,0 ± 0,76) and 12 h (9,33 ± 0,10 vs. 7,35 ± 0,15) of incubation. IL-10-/- animals showed greater contractile vascular response compared to the control group (9,33 ± 0,10 vs. 11,02 ± 0,24) and the incubation with Ang-(1-7), at 5 min and 12 h, was unable to modulate the contractile response in the absence of endogenous IL-10. Analysis of protein expression showed that incubation with Ang-(1-7) increased tissue expression of JAK1 at 24 h, and STAT3 expression at 5 min, 1 h, 6 h, 12 h and 24 h of incubation. In addition to modulating the precursors of the IL-10 signaling pathway, incubation with Ang-(1-7) increased tissue levels of this cytokine at 6 h, 12 h and 24 h of incubation. In the expression/activity of MKP-1, Ang- (1-7) increased its tissue expression after 12 h of incubation, except in animals IL-10-/- , which showed a reduction in the expression of MKP-1 in the vasculature. These results demonstrate that Ang-(1-7) is able to positively modulate the tissue levels of IL-10 and its precursors (JAK/STAT), as a consequence, it modulates the expression/activity of MKP-1 and the response of vascular contraction. Finally, considering the potential capacity of these mediators in vascular function, these results provide a new model for the performance and characterization of Ang-(1-7), via IL-10, in the contractile vascular response.