Human airway trypsin-like protease induces PAR-2-mediated IL-8 release in psoriasis vulgaris.
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.
Iwakiri
Kana
K
Department of Molecular Pathology, Institute of Gerontology, Graduate School of Medicine, Nippon Medical School, Kawasaki, Japan.
Ghazizadeh
Mohammad
M
Jin
Enjing
E
Fujiwara
Masakazu
M
Takemura
Tamiko
T
Takezaki
Shin-ichiro
S
Kawana
Seiji
S
Yasuoka
Susumu
S
Kawanami
Oichi
O
D000328:Adult; D000368:Aged; D001692:Biological Transport / Q000187:drug effects; D001706:Biopsy; D002455:Cell Division / Q000187:drug effects; D002478:Cells, Cultured; D004247:DNA / Q000096:biosynthesis; D004817:Epidermis / Q000378:metabolism / Q000473:pathology; D005260:Female; D006801:Humans; D020382:Interleukin-18 / Q000378:metabolism*; D015603:Keratinocytes / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D011565:Psoriasis / Q000378:metabolism* / Q000473:pathology; D012333:RNA, Messenger / Q000378:metabolism; D044464:Receptor, PAR-2 / Q000235:genetics / Q000378:metabolism*; D011994:Recombinant Proteins / Q000494:pharmacology; D012697:Serine Endopeptidases / Q000235:genetics / Q000378:metabolism* / Q000494:pharmacology; D012867:Skin / Q000378:metabolism / Q000473:pathology; D014018:Tissue Distribution
D020382:Interleukin-18; D012333:RNA, Messenger; D044464:Receptor, PAR-2; D011994:Recombinant Proteins; D004247:DNA; D012697:Serine Endopeptidases; C112256:human airway trypsin-like protease