Interleukin (IL)-6 modulates transforming growth factor-[beta] receptor I and II (TGF-[beta]RI and II) function in epidermal keratinocytes

• Published in: Experimental dermatology Vol. 26; no. 8; p. 697
• Main Authors: Luckett-Chastain, Lerin R, Cottrell, Mackenzie L, Kawar, Bethany M, Ihnat, Michael A, Gallucci, Randle M
• Format: Journal Article
• Language: English
• Published: Chichester Wiley Subscription Services, Inc 01.08.2017
• Subjects: Bromodeoxyuridine; Cell adhesion & migration; Cell migration; Epidermis; Fibroblasts; Flow cytometry; Immunoprecipitation; Interleukin 6; Keratinocytes; Localization; Phosphorylation; Polymerase chain reaction; Protein transport; Rodents; Signal transduction; Skin; Smad2 protein; Smad7 protein; Transforming growth factor-b
• ISSN: 0906-6705; 1600-0625
• DOI: 10.1111/exd.13260

It been shown that IL-6 modulates TGF-[beta]1 expression in fibroblasts, however, what role IL-6 plays concerning TGF-[beta]R 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-[beta] receptors in skin. Skin from WT,IL-6 over-expressing mice and IL-6 treated keratinocyte cultures was analysed for TGF-[beta]RI and TGF-[beta]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-[beta]RII expression in the epidermis. IL-6 treatment of keratinocytes induced TGF-[beta]RI and II expression and augmented TGF-[beta]1-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-[beta]RI and II expression and signal transduction via trafficking of the receptor to lipid raft pools.