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Type of publication: Journal Article
Type of document: Full Paper

Year: 2015

Authors: Stremnitzer, C; Manzano-Szalai, K; Willensdorfer, A; Starkl, P; Pieper, M; K├Ânig, P; Mildner, M; Tschachler, E; Reichart, U; Jensen-Jarolim, E

Title: Papain Degrades Tight Junction Proteins of Human Keratinocytes In Vitro and Sensitizes C57BL/6 Mice via the Skin Independent of its Enzymatic Activity or TLR4 Activation.

Source: J Invest Dermatol. 2015; 135(7):1790-1800

Authors Vetmeduni Vienna:

Jensen-Jarolim Erika
Reichart Ursula
Szalai Krisztina

Vetmed Research Units
Biomodels Austria
Messerli Research Institute, Comparative Medicine
Institute of Animal Breeding and Genetics, Unit of Molecular Genetics

Papain is commonly used in food, pharmaceutical, textile, and cosmetic industries and is known to induce occupational allergic asthma. We have previously shown that the papain-like cysteine protease Dermatophagoides pteronyssinus 1 from house dust mite exhibits percutaneous sensitization potential. We aimed here to investigate the potential of papain itself in epicutaneous sensitization. The effects of papain on tight junction (TJ) proteins were tested in vitro in human primary keratinocytes. Using C57BL/6 wild-type and Toll-like receptor 4 (TLR4)-deficient mice, we analyzed the sensitization potential of papain, its effects on the skin barrier, and immune cell recruitment. Our results show that papain affects the skin barrier by increasing transepidermal water loss, degrading TJ proteins and inducing vasodilation. When topically applied, papain exhibited a high epicutaneous inflammatory potential by recruiting neutrophils, mast cells, and CD3-positive cells and by induction of a TH2-biased antibody response. However, its high potency for specific sensitization via the skin was TLR4 independent and, in spite of its capacity to degrade epidermal TJ proteins, does not rely on its enzymatic function. From our data, we conclude that papain has all features to act as a strong allergen via the skin.

Keywords Pubmed: Animals
Blotting, Western
Cells, Cultured
Disease Models, Animal
Enzyme Activation
Enzyme-Linked Immunosorbent Assay
Fluorescent Antibody Technique
In Vitro Techniques
Keratinocytes/drug effects
Mast Cells/immunology
Mast Cells/metabolism
Mice, Inbred C57BL
Random Allocation
Skin/drug effects
Tight Junction Proteins/drug effects*
Tight Junction Proteins/immunology
Toll-Like Receptor 4/metabolism*

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