1. ^*Department of Molecular Pathology, Institute of Gerontology, Graduate School of Medicine, Nippon Medical School, Kawasaki, Japan
2. ^†Department of Dermatology, Nippon Medical School, Tokyo, Japan
3. ^‡Department of Surgical Pathology, Nippon Red Cross Center Hospital, Tokyo, Japan
4. ^§Department of Dermatology, Nippon Medical School Second Hospital, Kawasaki, Japan
5. ^¶Department of Nursing, School of Medical Sciences, University of Tokushima, Tokushima, Japan

Correspondence: O. Kawanami, Department of Molecular Pathology, Institute of Gerontology, Graduate School of Medicine, Nippon Medical School, Kosugi-cho, Nakahara-ku, Kawasaki, Japan. Email: kawanami@nms.ac.jp

Received 29 July 2003; Revised 31 October 2003; Accepted 18 November 2003.

Abstract

Human airway trypsin-like protease (HAT), a novel serine protease in the airways, enhances cell growth and IL-8 production. The expression and role of HAT in the skin however, is unknown. Immunofluorescence staining and reverse transcription (RT)-PCR were done to know HAT production in normal and psoriatic tissues and keratinocyte cell lines. Cell growth and/or IL-8 release analyses were made by bromo-deoxyuridine (BrdU) uptake and ELISA. Psoriatic epidermis showed more extensive immunofluorescence expression of HAT, and less extensive expression of protease-activated receptor (PAR)-2. RT-PCR demonstrated a higher HAT and a lesser PAR-2 mRNA expressions in psoriatic epidermis. Normal keratinocyte and epidermoid carcinoma cell lines expressed HAT and PAR-2 mRNA, and immortalized keratinocytes (HaCaT) expressed PAR-2, but not HAT mRNA. PAR-2 was detected along the keratinocyte surface in culture and became invisible upon HAT stimulation, suggesting a process of its internalization. HAT or PAR-2 activating peptide did not enhance BrdU uptake, but induced an IL-8 release. Treatment with HAT and IL-1 synergistically increased the effect of IL-8 release. Inhibition of PAR-2 resulted in a decreased HAT-induced IL-8 release. Thus, HAT might promote PAR-2-mediated IL-8 production to accumulate inflammatory cells in the epidermal layer of psoriasis.