?-arrestin2 Mediates the Arginine Vasopressin-Induced Expression of IL-1? in Murine Hearts

Background: Circulating levels of arginine vasopressin (AVP) are elevated during cardiac stress and this could be a factor in cardiac inflammation and fibrosis. Herein, we studied the effects of AVP on interleukin-1 beta (IL-1 beta) production and the role(s) of beta-arrestin2-dependent signaling in murine heart. Methods: The levels of IL-1 beta mRNA and protein in adult rat cardiofibroblasts (ARCFs) was measured using quantitative PCR and ELISA, respectively. The activity of beta-arrestin2 was manipulated using either pharmacologic inhibitors or through recombinant beta-arrestin2 over-expression. These experiments were conducted to determine the roles of beta-arrestin2 in the regulation of AVP-induced IL-1 beta and NLRP3 inflammasome production. The phosphorylation and activation of NF -KB induced by AVP was measured by immunoblotting. beta-arrestin2 knockout (KO) mice were used to investigate whether beta-arrestin2 mediated the AVP-induced production of IL-1 beta and NLRP3, as well as the phosphorylation of the NF -KB p65 subunitin mouse myocardium. Prism GraphPad software(version 8.0), was used for all statistical analyses. Results: AVP induced the expression of IL-1 beta in a time-dependent manner in ARCFs but not in cultured adult rat cardiomyocytes (ARCMs). The inhibition of NF -KB with pyrrolidinedithiocarbamic acid (PDTC) prevented the AVP-induced phosphorylation of NF -KB and production of IL-1 beta and NLRP3 in ARCFs. The deletion of beta-arrestin2 blocked the phosphorylation of p65 and the expression of NLRP3 and IL-1 beta induced by AVP in both mouse hearts and in ARCFs. Conclusions: AVP promotes IL-1 beta expression through beta-arrestin2-mediated NF -KB signaling in murine heart.