Interleukin (IL)-6 modulates transforming growth factor -β receptor I and II (TGF-βRI and II) function in epidermal keratinocytes

Abstract

It been shown that IL-6 modulates TGF-β1 expression in fibroblasts, however; what role IL-6 plays concerning TGF-βR expression and function in skin is unknown. Therefore, the aim of this study was to investigate the mechanism by which IL-6 might modulates TGF-β receptors in skin.

Skin from WT, IL-6 overexpressing mice, and IL-6 treated keratinocyte cultures were analyzed for TGF-βRI and TGF-βRII expression via histology, PCR, and flow cytometry. Receptor function was assessed by cell migration, bromodeoxyuridine (BrdU) proliferation assays, and Smad7 expression and Smad2/3 phosphorylation. Receptor localization within the membrane was determined by co-immunoprecipitation.

IL-6 overexpression and treatment increased TGF-βRII expression in the epidermis. IL-6 treatment of keratinocytes induced TGF-βRI and II expression, and augmented TGF-β1-induced function as demonstrated through increased migration and decreased proliferation. Additionally, IL-6 treatment of keratinocytes altered receptor activity as indicated by altered Smad2/3 phosphorylation and increased Smad7 and membrane localization.

These results suggest that IL-6 regulates keratinocyte function by modulating TGF-βRI and II expression and signal transduction via trafficking of the receptor to lipid raft pools.

This article is protected by copyright. All rights reserved.

http://ift.tt/2gaRvlw