RRC ID 42140
Author Iwakiri K, Ghazizadeh M, Jin E, Fujiwara M, Takemura T, Takezaki S, Kawana S, Yasuoka S, Kawanami O.
Title Human airway trypsin-like protease induces PAR-2-mediated IL-8 release in psoriasis vulgaris.
Journal J Invest Dermatol
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.
Volume 122(4)
Pages 937-44
Published 2004-4-1
DOI 10.1111/j.0022-202X.2004.22415.x
PII S0022-202X(15)30765-X
PMID 15102084
MeSH Adult Aged Biological Transport / drug effects Biopsy Cell Division / drug effects Cells, Cultured DNA / biosynthesis Epidermis / metabolism Epidermis / pathology Female Humans Interleukin-18 / metabolism* Keratinocytes / metabolism Male Middle Aged Psoriasis / metabolism* Psoriasis / pathology RNA, Messenger / metabolism Receptor, PAR-2 / genetics Receptor, PAR-2 / metabolism* Recombinant Proteins / pharmacology Serine Endopeptidases / genetics Serine Endopeptidases / metabolism* Serine Endopeptidases / pharmacology Skin / metabolism Skin / pathology Tissue Distribution
IF 7.143
Times Cited 44
Human and Animal Cells A431(RCB0202)