Possible molecular mechanisms to account for the involvement of tryptase in the pathogenesis of psoriasis.
Tryptase has been suggested to take part in the pathophysiology of psoriasis mainly through the production of C3a by cleaving C3. However, studies using tryptase preparations of high purity do not support this notion. Therefore, although tryptase is unanimously believed to be involved in the immunopathogenesis of psoriasis, no convincing mechanism has been proposed for its role. This paper proposes several mechanisms by which this enyme may exert its role in the pathobiology of psoriasis. Tryptase is a mitogen for epithelial cells and stimulates IL-8 production and ICAM-1 expression by these cells. It also induces the expression of mRNA for IL-1beta and IL-8 and stimulates the selective release of IL-8 from endothelial cells and TNF-alpha, IL-1beta, and IL-6 from lymphocytes and monocytes. Besides itself being a chemoattractant for neutrophils, tryptase activates mast cells and generates kinins from kininogen, thereby playing a crucial role in leukocyte infiltration into psoriatic lesions. This enzyme also induces leukocyte infiltration partly through activating endothelial PAR-2, which contributes to leukocyte rolling, adherence and recruitment by inducing the release of endothelial platelet-activating factor. Through activating PAR-2, tryptase could also trigger the development of Langerhans cells which play a crucial role in the pathophysiology of psoriasis. This enzyme is a mitogen for fibroblasts, which are probably involved in the pathophysiology of psoriasis through production of insulin-like growth factor-I (IGF-I). Tryptase is a gelatinase and also activates stromelysin-1 (MMP-3), thereby contributing to the disruption of psoriatic basement membrane and to the joint damage seen in psoriatic arthritis. Increase of tryptase levels following trauma could also provide a mechanism for Koebner phenomenon seen in psoriasis.
Namazi
M R
MR
Dermatology Department, Shiraz University of Medical Sciences, P.O.Box 71955-687, Shiraz, Iran. namazi_mr@yahoo.com
D000818:Animals; D015415:Biomarkers / Q000097:blood / Q000378:metabolism; D006801:Humans; D008407:Mast Cells / Q000201:enzymology / Q000276:immunology / Q000473:pathology; D011565:Psoriasis / Q000201:enzymology* / Q000209:etiology / Q000473:pathology*; D053802:Tryptases / Q000737:chemistry* / Q000502:physiology*
D015415:Biomarkers; D053802:Tryptases