Human airway trypsin-like protease induces PAR-2-mediated IL-8 release in psoriasis vulgaris.

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-1beta 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.

• Authors: Kana Iwakiri, Mohammad Ghazizadeh, Enjing Jin, Masakazu Fujiwara, Tamiko Takemura, Shin-ichiro Takezaki, Seiji Kawana, Susumu Yasuoka, Oichi Kawanami
• Journal: The Journal of investigative dermatology (J Invest Dermatol) Vol. 122 Issue 4 Pg. 937-44 (Apr 2004) ISSN: 0022-202X [Print] United States
• PMID: 15102084 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Interleukin-18
• RNA, Messenger
• Receptor, PAR-2
• Recombinant Proteins
• DNA
• Serine Endopeptidases
• human airway trypsin-like protease

Topics

• Adult
• Aged
• Biological Transport (drug effects)
• Biopsy
• Cell Division (drug effects)
• Cells, Cultured
• DNA (biosynthesis)
• Epidermis (metabolism, pathology)
• Female
• Humans
• Interleukin-18 (metabolism)
• Keratinocytes (metabolism)
• Male
• Middle Aged
• Psoriasis (metabolism, pathology)
• RNA, Messenger (metabolism)
• Receptor, PAR-2 (genetics, metabolism)
• Recombinant Proteins (pharmacology)
• Serine Endopeptidases (genetics, metabolism, pharmacology)
• Skin (metabolism, pathology)
• Tissue Distribution