Full-length IL-33 regulates Smad3 phosphorylation and gene transcription in a distinctive AP2-dependent manner.

ABSTRACT: IL-33 has emerged as a central mediator of immune, inflammatory, and fibrotic responses. Many studies have focused on mature IL-33, but elevated expression of the precursor, full-length IL-33 (FLIL33), has also been implicated in a spectrum of diseases, including tissue fibrosis. We previously reported and now confirmed that overexpression of FLIL33 induced phosphorylation of the key profibrotic signaling mediator of TGF-β, Smad3, in primary human lung fibroblasts from healthy donors and idiopathic pulmonary fibrosis patients. Presently, we demonstrate that FLIL33-induced Smad3 phosphorylation was not abrogated by anti-TGF-β antibody but was abrogated by ALK5/TGFBR1-specific and Smad3-specific inhibition, indicating that FLIL33 effect was independent of TGF-β but dependent on its receptor,

SUBMITTER: Luzina IG 

PROVIDER: S-EPMC8502490 | biostudies-literature | 2020 Nov

REPOSITORIES: biostudies-literature