Increased mast cell expression of PAR-2 in skin inflammatory diseases and release of IL-8 upon PAR-2 activation.
Mast cells are increasingly present in the lesional skin of chronic skin inflammatory diseases including psoriasis and basal cell carcinoma (BCC). It has previously been shown that proteinase-activated receptor (PAR)-2 is expressed by mast cells, and tryptase is a potent activator of this receptor. In this study, skin biopsies from both healthy-looking and lesional skin of patients with psoriasis and superficial spreading BCC were collected and the expression of PAR-2 immunoreactivity in tryptase-positive mast cells was analysed. PAR-2 expression was confirmed in vitro in different mast cell populations. Cord-blood derived mast cells (CBMC) were stimulated with a PAR-2 activating peptide, 2-furoyl-LIGRLO-NH(2). Consequently, IL-8 and histamine production was analysed in the supernatants. We observed a significant increase in the percentage of mast cells expressing PAR-2 in the lesional skin of psoriasis and BCC patients compared with the healthy-looking skin. HMC-1.2, LAD-2 and CBMC mast cells all expressed PAR-2 both intracellularly and on the cell surface. CBMC activation with the PAR-2 activating peptide resulted in an increased secretion of IL-8, but no histamine release was observed. Furthermore, both PAR-2 and IL-8 were co-localized to the same tryptase-positive mast cells in the lesional BCC skin. These results show that mast cells express increased levels of PAR-2 in chronic skin inflammation. Also, mast cells can be activated by a PAR-2 agonist to secrete IL-8, a chemokine which can contribute to the progress of inflammation.
Carvalho
Ricardo Filipe da Silva
RF
Clinical Immunology and Allergy Unit, Department of Medicine, Karolinska Institutet, Stockholm, Sweden.
Nilsson
Gunnar
G
Harvima
Ilkka Tapani
IT
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D002280:Basal Cell Carcinoma / Q000378:metabolism*; D005260:Female; D006801:Humans; D016209:Interleukin-8 / Q000378:metabolism; D008297:Male; D008407:Mast Cells / Q000378:metabolism*; D008875:Middle Aged; D011565:Psoriasis / Q000378:metabolism*; D044464:Receptor, PAR-2 / Q000378:metabolism*; D012878:Skin Neoplasms / Q000378:metabolism*; D015854:Up-Regulation; D055815:Young Adult
D016209:Interleukin-8; D044464:Receptor, PAR-2