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Proc Natl Acad Sci U S A. 2010 Dec 21;107(51):22249-54. doi: 10.1073/pnas.1009751108. Epub 2010 Dec 6.

Development of atopic dermatitis-like skin disease from the chronic loss of epidermal caspase-8.

Author information

1
Division of Biological Sciences, Section of Cell and Developmental Biology, School of Medicine, University of California at San Diego, La Jolla, CA 92093, USA.

Abstract

Atopic dermatitis is an inflammatory skin disease that affects approximately 20% of children worldwide. Left untreated, the barrier function of the skin is compromised, increasing susceptibility to dehydration and infection. Despite its prevalence, its multifactorial nature has complicated the unraveling of its etiology. We found that chronic loss of epidermal caspase-8 recapitulates many aspects of atopic dermatitis, including a spongiotic phenotype whereby intercellular adhesion between epidermal keratinocytes is disrupted, adversely affecting tissue architecture and function. Although spongiosis is generally thought to be secondary to edema, we found that suppression of matrix metalloproteinase-2 activity is sufficient to abrogate this defect. p38 MAPK induces matrix metalloproteinase-2 expression to cleave E-cadherin, which mediates keratinocyte cohesion in the epidermis. Thus, the conditional loss of caspase-8, which we previously found to mimic a wound response, can be used to gain insights into how these same wound-healing processes are commandeered in inflammatory skin diseases.

PMID:
21135236
PMCID:
PMC3009816
DOI:
10.1073/pnas.1009751108
[Indexed for MEDLINE]
Free PMC Article

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