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

Luckett-Chastain, Lerin R.; Cottrell, Mackenzie L.; Kawar, Bethany M.; Ihnat, Michael A.; Gallucci, Randle M.

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

Published Date:

Mar 08 2017

Source:

Exp Dermatol. 26(8):697-704.

Language:

English

[PDF-1.46 MB]

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.

Subject:

[+]

Pubmed ID:

27892604

Pubmed Central ID:

PMC5446936

Document Type:

Journal Article

Funding:

R01 GM067745/GM/NIGMS NIH HHS/United States ; R01 OH010241/OH/NIOSH CDC HHS/United States ;

Collection(s):

CDC Public Access

Main Document Checksum:

[+]

Supporting Files:

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