RIS-1/psoriasin expression in epithelial skin cells indicates their selective role in innate immunity and in inflammatory skin diseases including acne

ABSTRACT

Objective: RIS-1/psoriasin/S100A7 is an epithelial antimicrobial peptide, whose expression is upregulated in inflammatory skin diseases and is induced by retinoids. Its molecular expression was investigated in skin cell cultures and in skin specimens to better understand its role in inflammatory procedures of the pilosebaceous unit. Methods: rtPCR and northern blotting of RIS-1/psoriasin and the retinoid-metabolizing genes CYP26AI and CRABP-II were performed in cells cultures (keratinocytes, sebocytes, fibroblasts, endothelial cells, melanocytes, lymphocytes and prostate cells; native and treated with retinoids) and in situ hybridization in normal and inflamed skin (acne, psoriasis). Results: a) RIS-1/psoriasin is expressed in keratinocytes and fibroblasts in vitro and in keratinocytes of the stratum granulosum in vivo. Retinoids in vitro and inflammatory conditions in vivo increase the levels of RIS-1/psoriasin in keratinocytes (both), sebocytes (inflammation only) and fibroblasts (retinoids). Sebocytes and fibroblasts are the metabolically most active skin cells, since they can upregulate the expression of CRABP-II and CYP26AI, genes responsible for retinoid metabolism. Inflammation modifies the compartmentation of RIS-1/psoriasin in sebaceous glands and the follicular root sheaths. Conclusion: The present data indicate that anti-inflammatory treatment targeting the epithelial compartments of the skin, including such with antibacterial peptides, may be promising for inflammatory skin diseases.

KEYWORDS:

• RIS-1
• psoriasin
• acne
• keratinocytes
• sebocytes
• bacteria

Disclosure of potential conflicts of interest

No potential conflicts of interest were disclosed.

Acknowledgements

The skilled technical assistance of Holger Seltmann and Frank K. Jugert is gratefully acknowledged. The authors acknowledge Dr. Thomas Lawley, Emory University, Atlanta, GA, USA for providing the immortalized vascular endothelial cell line HMEC-1, and Dr. Amir Tavakkol, Viamet Pharmaceuticals, Durham, NC, USA for providing the RIS-1 hybridization probe.

Additional information

Funding

This work was supported by grants of the Deutsche Forschungsgemeinschaft (Zo 75/2–1 and SFB 174, C6) to C.C. Zouboulis.