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Interleukin‐6 modulates transforming growth factor‐β receptor II function and receptor compartmentalization in epidermal keratinocytes (1148.11)
Author(s) -
Chastain Lerin,
Cottrell Mackenzie,
Ihnat Mike,
Gallucci Randle
Publication year - 2014
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.28.1_supplement.1148.11
Subject(s) - caveolin 1 , transforming growth factor , microbiology and biotechnology , receptor , phosphorylation , lipid raft , tgf alpha , keratinocyte , epidermal growth factor receptor , chemistry , biology , cancer research , signal transduction , cell culture , biochemistry , genetics
IL‐6 and TGF‐ β mediate a broad range of biological responses including growth, differentiation, and migration. We have previously shown that IL‐6 modulates Tgf‐β1 expression in fibroblasts, however; what role IL‐6 plays concerning TGFβ‐RII expression and function in skin cells is unknown. Therefore, the aim of this study was to investigate the mechanism by which IL‐6 might modulate TGFβ‐RII in skin. Skin from WT and IL‐6 over‐expressing mice and IL‐6 treated keratinocyte cultures were analyzed for TGF‐βRII expression via immunohistology and western blot. TGF‐βRII function and activity was assessed by cell migration, proliferation, and Smad2/3 phosphorylation. TGF‐βRII membrane localization was determined by co‐immunoprecipitation. IL‐6 overexpression and IL‐6 treatment increased TGF‐βRII expression in epidermis and isolated keratinocytes respectively. IL‐6 treatment of keratinocytes augmented TGF‐β1 function as demonstrated through increased migration and decreased proliferation. TGF‐ βRII is down regulated when located within caveolin rich lipid rafts and co‐IP showed with IL‐6 treatment, association between TGF‐ βRII and caveolin increased resulting in decreased Smad2/3 phosphorylation. These results suggest that IL‐6 regulates TGF‐ β1 function by modulating TGF‐ βRII expression and increasing trafficking of the receptor to lipid raft pools. Grant Funding Source : NIH/NIGMS R01GM67745