title: Mast cell tryptase and photoaging: possible involvement in the degradation of extra cellular matrix and basement membrane proteins.
abstract: Mast cells are widely distributed in the connective tissue of the body, but are particularly prominent in tissues such as skin. An increased number of mast cells can be found in the dermis under inflammatory conditions and ultraviolet (UV) exposed skin. Previous investigations have identified matrix metalloproteinases (MMPs) as key enzymes in the degradation of extra cellular matrix (ECM). This study reports about the potential contribution of human mast cell tryptase as a new triggering enzyme in matrix degradation process. Recent studies suggest that mast cell-derived proteases can activate MMPs. We investigated both the degradation of cellular matrix components and activation of MMPs by human tryptase. Mast cells are increased in photoaged skin and the increase of mast cell tryptase in UV irradiated skin was confirmed. Human mast cell tryptase was purified from human tonsils by a series of standard chromatographic procedures. Degradation of collagen type I was achieved by incubation of human type I collagen with tryptase and the fragments were quantified by SDS-PAGE and staining with Coomassie Brilliant Blue 250-R (CBB). Treatment with tryptase resulted in the activation of proMMP-9 as revealed by gelatinolytic activity in type IV collagen zymography. When tryptase was incubated with human type IV collagen, gradual degradation of intact collagen was detected by Western blotting. Furthermore, type IV collagen degradation was observed in the basement membrane (BM) of a three-dimensional (3D) skin model. Degranulation of mast cells, which release tryptase, can activate MMPs and causes direct damage to ECM proteins. These findings strongly implicate that tryptase either alone or in conjunction with activation of MMPs, can participate in ECM damage and the possible destruction of BM leading to photoaging.
authors.affiliation: Department of Research and Development, Ichimaru Pharcos Co. Ltd, 318-1 Asagi, Motosu City, Gifu 501-0475, Japan. arunasiri@ichimaru.co.jp
authors.forename: Arunasiri
authors.initials: A
authors.lastname: Iddamalgoda
authors.forename: Quang Trong
authors.initials: QT
authors.lastname: Le
authors.forename: Kenichi
authors.initials: K
authors.lastname: Ito
authors.forename: Kiyotaka
authors.initials: K
authors.lastname: Tanaka
authors.forename: Hiroyuki
authors.initials: H
authors.lastname: Kojima
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Kido
mesh_terms: D000818:Animals; D001485:Basement Membrane / Q000378:metabolism*; D024042:Collagen Type I / Q000378:metabolism; D024141:Collagen Type IV / Q000378:metabolism; D004792:Enzyme Precursors / Q000378:metabolism; D016326:Extracellular Matrix Proteins / Q000378:metabolism*; D008297:Male; D020780:Matrix Metalloproteinase 9 / Q000378:metabolism; D008565:Membrane Proteins / Q000378:metabolism*; D051379:Mice; D008812:Mice, Hairless; D012867:Skin / Q000528:radiation effects; D015595:Skin Aging; D053802:Tryptases / Q000502:physiology*
chemical_list: D024042:Collagen Type I; D024141:Collagen Type IV; D004792:Enzyme Precursors; D016326:Extracellular Matrix Proteins; D008565:Membrane Proteins; D053802:Tryptases; C120487:pro-matrix metalloproteinase 9; D020780:Matrix Metalloproteinase 9