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

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.