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