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

Details

• Alternative Title:
  Exp Dermatol
• Personal Author:
  Luckett-Chastain, Lerin R. ; Cottrell, Mackenzie L. ; Kawar, Bethany M. ; Ihnat, Michael A. ; Gallucci, Randle M.
• Description:
  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.
• Keywords:
  Animals Animals, Newborn Caveolin Gene Knockout Techniques Interleukin-6 Keratinocytes Mice Migration Protein Serine-Threonine Kinases Receptor, Transforming Growth Factor-beta Type I Receptor, Transforming Growth Factor-beta Type II Receptor Endocytosis Receptors, Transforming Growth Factor Beta Skin Smad Smad Proteins

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• Source:
  Exp Dermatol. 26(8):697-704
• Pubmed ID:
  27892604
• Pubmed Central ID:
  PMC5446936
• Document Type:
  Journal Article
• Funding:
  R01 GM067745/GM/NIGMS NIH HHSUnited States/ ; R01 OH010241/OH/NIOSH CDC HHSUnited States/
• Volume:
  26
• Issue:
  8
• Collection(s):
  CDC Public Access
• Main Document Checksum:
  urn:sha256:aa592aca92844424315c59b0f8e83d968e5d6dd834c3804326f25fb87f583f88
• Download URL:
  https://stacks.cdc.gov/view/cdc/45934/cdc_45934_DS1.pdf
• File Type:
  [PDF - 1.46 MB ]