title: 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 over-expressing mice and IL-6 treated keratinocyte cultures was analysed 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.
authors.affiliation: Pharmaceutical Sciences Department, University of Oklahoma Health Science Center, Oklahoma City, OK, USA.
authors.forename: Lerin R
authors.initials: LR
authors.lastname: Luckett-Chastain
authors.affiliation: Pharmacotherapy and Experimental Therapeutics Division, UNC Eshelman School of Pharmacy, Chapel Hill, NC, USA.
authors.forename: Mackenzie L
authors.initials: ML
authors.lastname: Cottrell
authors.affiliation: Pharmaceutical Sciences Department, University of Oklahoma Health Science Center, Oklahoma City, OK, USA.
authors.forename: Bethany M
authors.initials: BM
authors.lastname: Kawar
authors.affiliation: Pharmaceutical Sciences Department, University of Oklahoma Health Science Center, Oklahoma City, OK, USA.
authors.forename: Michael A
authors.initials: MA
authors.lastname: Ihnat
authors.affiliation: Pharmaceutical Sciences Department, University of Oklahoma Health Science Center, Oklahoma City, OK, USA.
authors.forename: Randle M
authors.initials: RM
authors.lastname: Gallucci
mesh_terms: D000818:Animals; D000831:Animals, Newborn; D055786:Gene Knockout Techniques; D015850:Interleukin-6 / Q000378:metabolism*; D015603:Keratinocytes / Q000378:metabolism*; D051379:Mice; D017346:Protein Serine-Threonine Kinases / Q000378:metabolism*; D000077293:Receptor, Transforming Growth Factor-beta Type I; D000077294:Receptor, Transforming Growth Factor-beta Type II; D018125:Receptors, Transforming Growth Factor beta / Q000378:metabolism*; D051785:Smad Proteins / Q000378:metabolism
chemical_list: D015850:Interleukin-6; D018125:Receptors, Transforming Growth Factor beta; D051785:Smad Proteins; C577686:interleukin-6, mouse; D017346:Protein Serine-Threonine Kinases; D000077293:Receptor, Transforming Growth Factor-beta Type I; D000077294:Receptor, Transforming Growth Factor-beta Type II
keywords: caveolin; migration; receptor endocytosis; skin; smad