Proasthmatic effects and mechanisms of action of the dust mite allergen, Der p 1, in airway smooth muscle.

作者: Michael M. Grunstein , Haviva Veler , Xiaoyin Shan , Joshua Larson , Judith S. Grunstein

DOI: 10.1016/J.JACI.2005.03.046

关键词: ImmunologyHouse dust miteMechanism of actionPyroglyphidaeKinasep38 mitogen-activated protein kinasesMAPK/ERK pathwaySignal transductionBiologyMitogen-activated protein kinase kinase

摘要: Background House dust mite allergen exposure is a key risk factor for the development of allergic asthma. Beyond provoking immune cell-mediated responses, house allergens were recently shown to exert direct effects on airway structural cells secondary their intrinsic protease activities. Objective This study tested hypothesis that can produce changes in responsiveness through effect smooth muscle (ASM). Methods Isolated rabbit ASM tissues exposed allergen, Der p 1, and induced activation mitogen-activated protein kinase (MAPK) signaling pathways examined under different experimental conditions. Results The observations demonstrated following: (1) 1 elicited enhanced constrictor responses impaired relaxation tissues, (2) these proasthmatic-like attributed its cysteine activity, (3) associated with both extracellular signal-regulated (ERK) 1/2 p38 MAPK pathways. Additionally, specific blockade ERK1/2 was found prevent 1–induced responsiveness, whereas inhibition action latter result augmented ERK1/2. Conclusion These findings are first demonstrate directly elicit signaling, wherein proasthmatic by ERK1/2, coactivation exerts homeostatic negatively regulating signaling.

参考文章(39)
Cecile King, Geoffrey A. Stewart, Siobhan Brennan, Phillip J. Thompson, Dust Mite Proteolytic Allergens Induce Cytokine Release from Cultured Airway Epithelium Journal of Immunology. ,vol. 161, pp. 3645- 3651 ,(1998)
Catherine A. Hazzalin, Rozen Le Panse, Eva Cano, Louis C. Mahadevan, Anisomycin Selectively Desensitizes Signalling Components Involved in Stress Kinase Activation and fos and jun Induction Molecular and Cellular Biology. ,vol. 18, pp. 1844- 1854 ,(1998) , 10.1128/MCB.18.4.1844
Linda S. Chambers, Judith L. Black, Philip Poronnik, Peter R. A. Johnson, Functional effects of protease-activated receptor-2 stimulation on human airway smooth muscle. American Journal of Physiology-lung Cellular and Molecular Physiology. ,vol. 281, ,(2001) , 10.1152/AJPLUNG.2001.281.6.L1369
FABIEN SCHMIDLIN, SILVIA AMADESI, REYNAL VIDIL, MARCELLO TREVISANI, NADINE MARTINET, GEORGE CAUGHEY, MICHELE TOGNETTO, GIORGIO CAVALLESCO, CRISTINA MAPP, PIERANGELO GEPPETTI, NIGEL W. BUNNETT, Expression and function of proteinase-activated receptor 2 in human bronchial smooth muscle. American Journal of Respiratory and Critical Care Medicine. ,vol. 164, pp. 1276- 1281 ,(2001) , 10.1164/AJRCCM.164.7.2101157
Henk F. Kauffman, J.F.Chris Tomee, Marjolein A. van de Riet, Andre J.B. Timmerman, Peter Borger, Protease-dependent activation of epithelial cells by fungal allergens leads to morphologic changes and cytokine production. The Journal of Allergy and Clinical Immunology. ,vol. 105, pp. 1185- 1193 ,(2000) , 10.1067/MAI.2000.106210
Rommel S Lan, Darryl A Knight, Geoff A Stewart, Peter J Henry, Role of PGE2 in protease-activated receptor-1, -2 and -4 mediated relaxation in the mouse isolated trachea British Journal of Pharmacology. ,vol. 132, pp. 93- 100 ,(2001) , 10.1038/SJ.BJP.0703776
Annette B. Rice, Jennifer L. Ingram, James C. Bonner, p38 mitogen-activated protein kinase regulates growth factor-induced mitogenesis of rat pulmonary myofibroblasts. American Journal of Respiratory Cell and Molecular Biology. ,vol. 27, pp. 759- 765 ,(2002) , 10.1165/RCMB.2002-0070OC
Tony R. Bai, , Abnormalities in airway smooth muscle in fatal asthma. The American review of respiratory disease. ,vol. 141, pp. 552- 557 ,(1990) , 10.1164/AJRCCM/141.3.552
Terrance A. Stadheim, Gregory L. Kucera, Extracellular signal-regulated kinase (ERK) activity is required for TPA-mediated inhibition of drug-induced apoptosis. Biochemical and Biophysical Research Communications. ,vol. 245, pp. 266- 271 ,(1998) , 10.1006/BBRC.1998.8410