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

Christopher Li, Samuel Lasse, Pedro Lee, Manando Nakasaki, Shih Wei Chen, Kenshi Yamasaki, Richard L. Gallo, Colin Jamora

Research output: Contribution to journalArticlepeer-review

58 Citations (Scopus)

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 Ecadherin, 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.

Original languageEnglish
Pages (from-to)22249-22254
Number of pages6
JournalProceedings of the National Academy of Sciences of the United States of America
Volume107
Issue number51
DOIs
Publication statusPublished - 2010 Dec 21
Externally publishedYes

ASJC Scopus subject areas

  • General

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