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Interleukin ( IL )‐6 modulates transforming growth factor‐β receptor I and II ( TGF ‐β RI and II ) function in epidermal keratinocytes
Author(s) -
LuckettChastain Lerin R.,
Cottrell Mackenzie L.,
Kawar Bethany M.,
Ihnat Michael A.,
Gallucci Randle M.
Publication year - 2017
Publication title -
experimental dermatology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.108
H-Index - 96
eISSN - 1600-0625
pISSN - 0906-6705
DOI - 10.1111/exd.13260
Subject(s) - keratinocyte , receptor , transforming growth factor , signal transduction , r smad , flow cytometry , microbiology and biotechnology , phosphorylation , chemistry , biology , tgf alpha , epidermal growth factor receptor , biochemistry , in vitro
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 over‐expressing mice and IL ‐6 treated keratinocyte cultures was analysed for TGF ‐β RI and TGF ‐β RII 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 ‐β RII expression in the epidermis. IL ‐6 treatment of keratinocytes induced TGF ‐β RI 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 ‐β RI and II expression and signal transduction via trafficking of the receptor to lipid raft pools.