Document Detail


Collagen XVII (BP180) modulates keratinocyte expression of the proinflammatory chemokine, IL-8.
MedLine Citation:
PMID:  22775995     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
Collagen XVII (COL17), a transmembrane protein expressed in epidermal keratinocytes (EK), is targeted by pathogenic autoantibodies in bullous pemphigoid. Treatment of EK with anti-COL17 autoantibodies triggers the production of proinflammatory cytokines. In this study, we test the hypothesis that COL17 is involved in the regulation of the EK proinflammatory response, using IL-8 expression as the primary readout. The absence of COL17 in EK derived from a junctional epidermolysis bullosa patient or shRNA-mediated knockdown of COL17 in normal EK resulted in a dysregulation of IL-8 responses under various conditions. The COL17-deficient cells showed an abnormally high IL-8 response after treatment with lipopolysaccharide (LPS), ultraviolet-B radiation or tumor necrosis factor, but exhibited a blunted IL-8 response to phorbol 12-myristate 13-acetate exposure. Induction of COL17 expression in COL17-negative EK led to a normalization of the LPS-induced proinflammatory response. Although α6β4 integrin was found to be up-regulated in COL17-deficient EK, siRNA-mediated knockdown of the α6 and β4 subunits revealed that COL17's effects on the LPS IL-8 response are not dependent on this integrin. In LPS-treated cells, inhibition of NF-kappa B activity in COL17-negative EK resulted in a normalization of their IL-8 response, and expression of an NF-kappa B-driven reporter was shown to be higher in COL17-deficient, compared with normal EK. These findings support the hypothesis that COL17 plays an important regulatory role in the EK proinflammatory response, acting largely via NF-kappa B. Future investigations will focus on further defining the molecular basis of this novel control network.
Authors:
Françoise Van den Bergh; Steven L Eliason; Brian T Burmeister; George J Giudice
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Publication Detail:
Type:  Comparative Study; Journal Article; Research Support, N.I.H., Extramural    
Journal Detail:
Title:  Experimental dermatology     Volume:  21     ISSN:  1600-0625     ISO Abbreviation:  Exp. Dermatol.     Publication Date:  2012 Aug 
Date Detail:
Created Date:  2012-07-10     Completed Date:  2012-10-29     Revised Date:  2013-08-12    
Medline Journal Info:
Nlm Unique ID:  9301549     Medline TA:  Exp Dermatol     Country:  Denmark    
Other Details:
Languages:  eng     Pagination:  605-11     Citation Subset:  IM    
Copyright Information:
© 2012 John Wiley & Sons A/S.
Affiliation:
Division of Rheumatology, Medical College of Wisconsin, Milwaukee, WI, USA.
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MeSH Terms
Descriptor/Qualifier:
Autoantigens / genetics,  metabolism*
Cell Line
Epidermolysis Bullosa / metabolism*,  pathology
Gene Expression Regulation / drug effects
Humans
Inflammation / metabolism*,  pathology
Integrin alpha6beta4 / metabolism
Interleukin-18 / metabolism*
Keratinocytes / drug effects,  metabolism*,  radiation effects
Lipopolysaccharides / pharmacology
NF-kappa B / metabolism
Non-Fibrillar Collagens / deficiency,  genetics,  metabolism*
RNA, Small Interfering / pharmacology
Tetradecanoylphorbol Acetate / pharmacology
Tumor Necrosis Factor-alpha / pharmacology
Ultraviolet Rays
Grant Support
ID/Acronym/Agency:
K01 AR048901/AR/NIAMS NIH HHS; K01-AR048901/AR/NIAMS NIH HHS; R01 AR040410/AR/NIAMS NIH HHS; R01-AR040410/AR/NIAMS NIH HHS; R21 AI076731/AI/NIAID NIH HHS; R21-AI076731/AI/NIAID NIH HHS
Chemical
Reg. No./Substance:
0/Autoantigens; 0/Integrin alpha6beta4; 0/Interleukin-18; 0/Lipopolysaccharides; 0/NF-kappa B; 0/Non-Fibrillar Collagens; 0/RNA, Small Interfering; 0/Tumor Necrosis Factor-alpha; 0/collagen type XVII; 16561-29-8/Tetradecanoylphorbol Acetate
Comments/Corrections

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