Work

Transcriptional regulation of the IL-13Rα2 gene in human lung fibroblasts

Year: 2020

Type: article

Abstract: Interleukin (IL)−13 is a type 2 cytokine with important roles in allergic diseases, asthma, and tissue fibrosis. Its receptor (R) α1 is primarily responsible for the biological actions of this cytokine, while Rα2 possesses a decoy function which can block IL-13 signaling. Although the expression of Rα2 is known to be subject to modulation, information about its transcriptional regulation is limited. In this study, we sought to expand the understanding of transcriptional control of Rα2 in lung fibroblasts. We confirmed previous reports that IL-13 elicited modest induction of Rα2 in normal adult human lung fibroblasts, but found that prostaglandin E2(PGE2) and fibroblast growth factor 2 (FGF-2) –mediators known to influence fibroblast activation in tissue fibrosis but not previously investigated in this regard – led to a much greater magnitude of Rα2 induction. Although both PGE2(via protein kinase A) and FGF-2 (via protein kinase B, also known as AKT) depended on activation of cAMP-responsive element-binding protein (CREB) for induction of Rα2 expression, they nevertheless demonstrated synergy in doing so, likely attributable to their differential utilization of distinct transcriptional start sites on the Rα2 promoter. Our data identify CREB activation via PGE2and FGF-2 as a previously unrecognized molecular controller of Rα2 gene induction and provide potential new insights into strategies for therapeutic manipulation of this endogenous brake on IL-13 signaling.

Source: Scientific Reports

DOI: 10.1038/s41598-020-57972-1