Interleukin (IL)-6 Modulates Transforming Growth Factor-Β Receptor I and II (TGF-βRI and II) Function in Epidermal Keratinocytes

Details

• Personal Author:
  Cottrell ML ; Gallucci RM ; Ihnat MA ; Kawar BM ; Luckett-Chastain LR
• Description:
  It been shown that IL-6 modulates TGF-beta1 expression in fibroblasts, however, what role IL-6 plays concerning TGF-betaR 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-betaRI and TGF-betaRII 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-betaRII expression in the epidermis. IL-6 treatment of keratinocytes induced TGF-betaRI and II expression and augmented TGF-beta1-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-betaRI and II expression and signal transduction via trafficking of the receptor to lipid raft pools. [Description provided by NIOSH]
• Subjects:
  Animals Energy Metabolism Environmental Exposure Genetics Histology Laboratories Occupational Health Safety Skin
• Keywords:
  Author Keywords: Skin Caveolin Dermal Exposures Exposure Levels Fibroblasts Genes Laboratory Animals Metabolism Migration Proteins Receptor Endocytosis Skin Exposure Smad

  More +
• ISSN:
  0906-6705
• Document Type:
  Text
• Funding:
  Grant
• Genre:
  Journal Article
• Place as Subject:
  North Carolina ; Oklahoma ; OSHA Region 4 ; OSHA Region 6
• CIO:
  National Institute for Occupational Safety and Health (NIOSH)
• Topic:
  Workplace Safety & Health
• Location:
  North America
• Volume:
  26
• Issue:
  8
• NIOSHTIC Number:
  nn:20051414
• Citation:
  Exp Dermatol 2017 Aug; 26(8):697-704
• Contact Point Address:
  Randle M. Gallucci, OUHSC College of Pharmacy, Oklahoma City, OK 73117
• Email:
  randy-gallucci@ouhsc.edu
• Federal Fiscal Year:
  2017
• NORA Priority Area:
  Manufacturing ; Oil and Gas Extraction
• Performing Organization:
  University of Oklahoma Health Sciences Center, Oklahoma City
• Peer Reviewed:
  False
• Start Date:
  20130901
• Source Full Name:
  Experimental Dermatology
• End Date:
  20180831
• Collection(s):
  National Institute for Occupational Safety and Health
• Main Document Checksum:
  urn:sha-512:f7089046df4d0aee7fead53ba2cb59a97de64ddee2b061515bdad498bd12fc7d21406e5a895c72f541a7c7232da35d9da1e7b5f0910b3d6d82957c5871ce2d1e
• Download URL:
  https://stacks.cdc.gov/view/cdc/211381/cdc_211381_DS1.pdf
• File Type:
  [PDF - 836.44 KB ]