Journal article
Collagen XVII (BP180) modulates keratinocyte expression of the proinflammatory chemokine, IL-8
Experimental dermatology, Vol.21(8), pp.605-611
08/2012
DOI: 10.1111/j.1600-0625.2012.01529.x
PMCID: PMC3395233
PMID: 22775995
Abstract
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 a6 beta 4 integrin was found to be up-regulated in COL17-deficient EK, siRNA-mediated knockdown of the a6 and beta 4 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.
Details
- Title: Subtitle
- Collagen XVII (BP180) modulates keratinocyte expression of the proinflammatory chemokine, IL-8
- Creators
- Francoise Van den Bergh - Medical College of WisconsinSteven L. Eliason - University of IowaBrian T. Burmeister - University of IowaGeorge J. Giudice - University of Iowa
- Resource Type
- Journal article
- Publication Details
- Experimental dermatology, Vol.21(8), pp.605-611
- DOI
- 10.1111/j.1600-0625.2012.01529.x
- PMID
- 22775995
- PMCID
- PMC3395233
- NLM abbreviation
- Exp Dermatol
- ISSN
- 0906-6705
- eISSN
- 1600-0625
- Publisher
- Wiley
- Number of pages
- 7
- Grant note
- R21AI076731 / NATIONAL INSTITUTE OF ALLERGY AND INFECTIOUS DISEASES; United States Department of Health & Human Services; National Institutes of Health (NIH) - USA; NIH National Institute of Allergy & Infectious Diseases (NIAID) R01AR040410 / NATIONAL INSTITUTE OF ARTHRITIS AND MUSCULOSKELETAL AND SKIN DISEASES; United States Department of Health & Human Services; National Institutes of Health (NIH) - USA; NIH National Institute of Arthritis & Musculoskeletal & Skin Diseases (NIAMS) R01-AR040410; K01-AR048901; R21- AI076731 / National Institutes of Health (USA); United States Department of Health & Human Services; National Institutes of Health (NIH) - USA
- Language
- English
- Date published
- 08/2012
- Academic Unit
- Anatomy and Cell Biology
- Record Identifier
- 9984622051502771
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