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Interleukin-1, inflammasomes and the skin


Feldmeyer, L; Werner, S; French, L E; Beer, H D (2010). Interleukin-1, inflammasomes and the skin. European Journal of Cell Biology, 89(9):638-444.

Abstract

Interleukin (IL)-1 is a highly active and pleiotropic pro-inflammatory cytokine. Recent data impressively demonstrate that activating mutations in a human gene involved in proIL-1beta maturation or loss-of-function mutations in the gene encoding IL-1 receptor antagonist (IL-1Ra) cause excessive activity of this cytokine. This can result in life-threatening systemic and local inflammation, particularly in the skin. Interestingly, experiments in mice revealed that epidermal keratinocytes can secrete large amounts of IL-1alpha, which induces an inflammatory response in the skin. Secretion of IL-1 requires caspase-1 activity, and activation of the protease takes place in innate immune complexes, called inflammasomes. As keratinocytes express and activate caspase-1 in an inflammasome-dependent manner, these epithelial cells might be critically involved in the innate immunity of the skin. In this review we summarize the current knowledge on IL-1 and inflammasomes in the skin, particularly their involvement in skin homeostasis and disease. In addition, we discuss the hypothesis that keratinocytes are not only static bricks of the epidermal wall, but immunologically active cells critically involved in different (auto)-inflammatory (skin) diseases.

Abstract

Interleukin (IL)-1 is a highly active and pleiotropic pro-inflammatory cytokine. Recent data impressively demonstrate that activating mutations in a human gene involved in proIL-1beta maturation or loss-of-function mutations in the gene encoding IL-1 receptor antagonist (IL-1Ra) cause excessive activity of this cytokine. This can result in life-threatening systemic and local inflammation, particularly in the skin. Interestingly, experiments in mice revealed that epidermal keratinocytes can secrete large amounts of IL-1alpha, which induces an inflammatory response in the skin. Secretion of IL-1 requires caspase-1 activity, and activation of the protease takes place in innate immune complexes, called inflammasomes. As keratinocytes express and activate caspase-1 in an inflammasome-dependent manner, these epithelial cells might be critically involved in the innate immunity of the skin. In this review we summarize the current knowledge on IL-1 and inflammasomes in the skin, particularly their involvement in skin homeostasis and disease. In addition, we discuss the hypothesis that keratinocytes are not only static bricks of the epidermal wall, but immunologically active cells critically involved in different (auto)-inflammatory (skin) diseases.

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Additional indexing

Item Type:Journal Article, refereed, original work
Communities & Collections:04 Faculty of Medicine > University Hospital Zurich > Dermatology Clinic
Dewey Decimal Classification:610 Medicine & health
Language:English
Date:2010
Deposited On:09 Jan 2011 09:10
Last Modified:07 Dec 2017 05:35
Publisher:Elsevier
ISSN:0171-9335
Publisher DOI:https://doi.org/10.1016/j.ejcb.2010.04.008
PubMed ID:20605059

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