Skip Navigation
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

National Institute of Environmental Health Sciences

Use this QR code to view the newest version of this document

Your Environment. Your Health.

Publication Detail

Title: SERPINB3/B4 contributes to early inflammation and barrier dysfunction in an experimental murine model of atopic dermatitis.

Authors: Sivaprasad, Umasundari; Kinker, Kayla G; Ericksen, Mark B; Lindsey, Mark; Gibson, Aaron M; Bass, Stacey A; Hershey, Nicolas S; Deng, Jingyuan; Medvedovic, Mario; Khurana Hershey, Gurjit K

Published In J Invest Dermatol, (2015 Jan)

Abstract: Serine proteases are critical for epidermal barrier homeostasis, and their aberrant expression and/or activity is associated with chronic skin diseases. Elevated levels of the serine protease inhibitors SERPINB3 and SERPINB4 are seen in patients with atopic dermatitis and psoriasis. However, their mechanistic role in the skin is unknown. To evaluate the contribution of Serpinb3a (mouse homolog of SERPINB3 and SERPINB4) in atopic dermatitis, we examined the effect of topical Aspergillus fumigatus extract exposure in wild-type and Serpinb3a-null mice on transepidermal water loss (TEWL), sensitization, and inflammation. Allergen exposure induced Serpinb3a expression in the skin, along with increased TEWL, epidermal thickness, and skin inflammation, all of which were attenuated in the absence of Serpinb3a. Attenuated TEWL correlated with decreased expression of the pro-inflammatory marker S100A8. Silencing of SERPINB3/B4 in human keratinocytes decreased S100A8 expression, supporting a role for SERPINB3/B4 in the initiation of the acute inflammatory response. RNA-seq analysis following allergen exposure identified a network of pro-inflammatory genes induced in wild-type mice that was absent in Serpinb3a-null mice. In conclusion, Serpinb3a deficiency attenuates barrier dysfunction and the early inflammatory response following cutaneous allergen exposure, supporting a role for Serpinb3a (mice) and SERPINB3/B4 (humans) early in atopic dermatitis.

PubMed ID: 25111616 Exiting the NIEHS site

MeSH Terms: Acute Disease; Animals; Antigens, Neoplasm/genetics; Antigens, Neoplasm/immunology*; Antigens, Neoplasm/metabolism; Aspergillus fumigatus/immunology; Calgranulin A/genetics; Calgranulin A/immunology; Calgranulin A/metabolism; Chronic Disease; Dermatitis, Atopic/genetics; Dermatitis, Atopic/immunology*; Dermatitis, Atopic/metabolism; Disease Models, Animal; Epidermis/immunology; Epidermis/metabolism; Gene Expression/immunology; Humans; Keratinocytes/immunology; Keratinocytes/metabolism; Mice, Inbred BALB C; Mice, Knockout; Serpins/genetics; Serpins/immunology*; Serpins/metabolism; Water Loss, Insensible/immunology

Back
to Top
Last Reviewed: October 07, 2024