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Inflamm Res. 2017 Aug;66(8):679-690. doi: 10.1007/s00011-017-1049-z. Epub 2017 Apr 22.

Involvement of Fas/FasL pathway in the murine model of atopic dermatitis.

Author information

1
Department of Regenerative Medicine, Military Institute of Hygiene and Epidemiology, Kozielska 4, 01-163, Warsaw, Poland.
2
Department of Pathology and Veterinary Diagnostics, Faculty of Veterinary Medicine, Warsaw University of Life Sciences, Nowoursynowska 159c, 02-776, Warsaw, Poland.
3
Department of Genetics and Animal Breeding, Faculty of Animal Science, Warsaw University of Life Sciences, Ciszewskiego 8, 02-786, Warsaw, Poland.
4
Museum and Institute of Zoology, Polish Academy of Science, Wilcza 64, 00-679, Warsaw, Poland.
5
Department of Regenerative Medicine, Military Institute of Hygiene and Epidemiology, Kozielska 4, 01-163, Warsaw, Poland. krzyzowskam@yahoo.com.

Abstract

OBJECTIVE AND DESIGN:

The aim of this study was to elucidate the role of apoptosis mediated through Fas/FasL pathway using the mouse model of atopic dermatitis (AD).

MATERIALS AND TREATMENT:

AD was induced by epicutaneous application of ovalbumin (OVA) in wild-type C57BL/6, B6. MRL-Faslpr/J (Fas-) and B6Smn.C3-Faslgld/J (FasL-) mouse strains.

METHODS:

Skin samples were subjected to staining for Fas/FasL expression, M30 epitope and assessment of inflammatory response via immunohistochemical staining. Cytokine and chemokine production was assessed by real-time PCR.

RESULTS:

In comparison to wild-type mice, OVA sensitization of Fas- and FasL-deficient mice led to increased epidermal and dermal thickness, collagen deposition and local inflammation consisting of macrophages, neutrophils and CD4+ T cells. Fas- and FasL-deficient mice showed increased total counts of regulatory T cells (Tregs) and IgE levels in blood as well as increased expression of IL-1β, IL-4, IL-5, IL-13 and TGF-1β mRNA in comparison to wild-type mice. On the other hand, expression of CXCL9 and CXCL10, IL-17 mRNAs in the skin samples in Fas- and FasL-deficient mice was decreased.

CONCLUSIONS:

Our results show that lack of the Fas-induced apoptosis leads to exacerbation of AD characteristics such as Th2 inflammation and dermal thickening. Therefore, Fas receptor can play an important role in AD pathogenesis by controlling development of the local inflammation.

KEYWORDS:

Apoptosis; Atopic dermatitis; Fas/FasL; Inflammation; Ovalbumin

PMID:
28434120
PMCID:
PMC5501908
DOI:
10.1007/s00011-017-1049-z
[Indexed for MEDLINE]
Free PMC Article

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