Tatler Amanda L, Porte Joanne, Knox Alan, Jenkins Gisli, Pang Linhua
Centre for Respiratory Research, Clinical Sciences Building, City Hospital, University of Nottingham, Hucknall Road, Nottingham NG5 1PB, UK.
Biochem Biophys Res Commun. 2008 May 30;370(2):239-42. doi: 10.1016/j.bbrc.2008.03.064. Epub 2008 Mar 24.
Transforming growth factor beta (TGFbeta) is a key remodelling factor in asthma. It is produced as a latent complex and the main limiting step in TGFbeta bioavailability is its activation. Mast cell tryptase has been shown to stimulate the release of functionally active TGFbeta from human airway smooth muscle (ASM) cells [P. Berger, P.O. Girodet, H. Begueret, O. Ousova, D.W. Perng, R. Marthan, A.F. Walls, J.M. Tunon de Lara, Tryptase-stimulated human airway smooth muscle cells induce cytokine synthesis and mast cell chemotaxis, FASEB J. 17 (2003) 2139-2141]. The aim of this study was to determine if tryptase could cause TGFbeta activation as well as expression in ASM cells via its receptor, proteinase-activated receptor 2 (PAR2). Tryptase caused TGFbeta activation without affecting levels of total TGFbeta. This effect was inhibited by the selective tryptase inhibitor FUT175 and leupeptin but not mimicked by the PAR2 activating peptide SLIGKV-NH(2). Furthermore, the ASM cells used in the study did not express PAR2. The results indicate that tryptase activates TGFbeta via a PAR2-independent proteolytic mechanism in human ASM cells and may help understanding the role of tryptase in asthma.
转化生长因子β（TGFβ）是哮喘中的关键重塑因子。它以潜伏复合物的形式产生，TGFβ生物利用度的主要限制步骤是其激活。肥大细胞类胰蛋白酶已被证明可刺激人气道平滑肌（ASM）细胞释放功能活性TGFβ[P. 伯杰，P.O. 吉罗代，H. 贝盖雷，O. 乌索娃，D.W. 彭，R. 马尔坦，A.F. 沃尔斯，J.M. 图农·德·拉拉，类胰蛋白酶刺激的人气道平滑肌细胞诱导细胞因子合成和肥大细胞趋化性，《美国实验生物学会联合会杂志》17（2003年）2139 - 2141]。本研究的目的是确定类胰蛋白酶是否能通过其受体蛋白酶激活受体2（PAR2）在ASM细胞中引起TGFβ激活以及表达。类胰蛋白酶导致TGFβ激活而不影响总TGFβ水平。这种效应被选择性类胰蛋白酶抑制剂FUT175和亮抑酶肽抑制，但未被PAR2激活肽SLIGKV - NH₂模拟。此外，研究中使用的ASM细胞不表达PAR2。结果表明，类胰蛋白酶通过人ASM细胞中不依赖PAR2的蛋白水解机制激活TGFβ，这可能有助于理解类胰蛋白酶在哮喘中的作用。
