Bronchial epithelium as a target for innovative treatments in asthma

被引:129
作者
Gras, Delphine [1 ]
Chanez, Pascal [1 ,2 ]
Vachier, Isabelle [3 ]
Petit, Aurelie [3 ,4 ]
Bourdin, Arnaud [3 ,4 ]
机构
[1] Univ Aix Marseille, CNRS, INSERM, U1067,UMR 7333, Marseille F-13015, France
[2] AP HM Hop Nord, Clin Bronches Allergie & Sommeil, Marseille, France
[3] CHRU Montpellier, Dept Resp Dis, Montpellier, France
[4] Univ Montpellier 1 & 2, INSERM, U1046, Montpellier, France
关键词
Asthma; Epithelial cells; Airways; Treatment; Structural changes; EPIDERMAL-GROWTH-FACTOR; THYMIC STROMAL LYMPHOPOIETIN; TOLL-LIKE RECEPTOR; NECROSIS-FACTOR-ALPHA; FC-EPSILON-RI; NICOTINIC ACETYLCHOLINE-RECEPTOR; NONNEURONAL CHOLINERGIC SYSTEM; INDUCED AIRWAY INFLAMMATION; GOBLET CELL HYPERPLASIA; CILIARY BEAT FREQUENCY;
D O I
10.1016/j.pharmthera.2013.07.008
中图分类号
R9 [药学];
学科分类号
1007 ;
摘要
Increasing evidence of a critical role played by the bronchial epithelium in airway homeostasis is opening new therapeutic avenues. Its unique situation at the interface with the environment suggests that the subtle regulation orchestrated by the epithelium between tolerance and specific immune response might be impaired in asthma. Airway mucus is acting as a physical and a biological fluid between the environment and the epithelium, synergistically moved by the cilia. In asthma, excessive mucus production is a hallmark of airway remodeling. Since many years we tried to therapeutically target mucus hypersecretion, but actually this option is still not achieved. The present review discusses the dynamic processes regulating airway mucus production. Airway inflammation is central in current asthma management Understanding of how the airway epithelium influences the TH2 paradigm in response to deleterious agents is improving. The multiple receptors expressed by the airway epithelium are the transducers of the biological signals induced by various invasive agents to develop the most adapted response. Airway remodeling is observed in severe chronic airway diseases and may result from ongoing disturbance of signal transduction and epithelial renewal. Chronic airway diseases such as asthma will require assessment of these epithelial abnormalities to identify phenotypic characteristics associated with predicting a clinical benefit for epithelial-directed therapies. (C) 2013 Elsevier Inc. All rights reserved.
引用
收藏
页码:290 / 305
页数:16
相关论文
共 311 条
[91]   Cluster analysis and clinical asthma phenotypes [J].
Haldar, Pranab ;
Pavord, Ian D. ;
Shaw, Dominic E. ;
Berry, Michael A. ;
Thomas, Michael ;
Brightling, Christopher E. ;
Wardlaw, Andrew I. ;
Green, Ruth H. .
AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE, 2008, 178 (03) :218-224
[92]  
Hamilos DL, 2001, J ALLERGY CLIN IMMUN, V108, P59
[93]   The role of the epidermal growth factor receptor in sustaining neutrophil inflammation in severe asthma [J].
Hamilton, LM ;
Torres-Lozano, C ;
Puddicombe, SM ;
Richter, A ;
Kimber, I ;
Dearman, RJ ;
Vrugt, B ;
Aalbers, R ;
Holgate, ST ;
Djukanovic, R ;
Wilson, SJ ;
Davies, DE .
CLINICAL AND EXPERIMENTAL ALLERGY, 2003, 33 (02) :233-240
[94]   Putative mediator role of endothelin-1 in asthma and other lung diseases [J].
Hay, DWP .
CLINICAL AND EXPERIMENTAL PHARMACOLOGY AND PHYSIOLOGY, 1999, 26 (02) :168-171
[95]   Endothelin receptors and calcium translocation pathways in human airways [J].
Hay, DWP ;
Luttmann, MA ;
Muccitelli, RM ;
Goldie, RG .
NAUNYN-SCHMIEDEBERGS ARCHIVES OF PHARMACOLOGY, 1999, 359 (05) :404-410
[96]   Endothelin-1: An interesting peptide or an important mediator in pulmonary diseases? [J].
Hay, DWP .
PULMONARY PHARMACOLOGY & THERAPEUTICS, 1998, 11 (2-3) :141-146
[97]   The innate immune response to bacterial flagellin is mediated by Toll-like receptor 5 [J].
Hayashi, F ;
Smith, KD ;
Ozinsky, A ;
Hawn, TR ;
Yi, EC ;
Goodlett, DR ;
Eng, JK ;
Akira, S ;
Underhill, DM ;
Aderem, A .
NATURE, 2001, 410 (6832) :1099-1103
[98]   Species-specific recognition of single-stranded RNA via toll-like receptor 7 and 8 [J].
Heil, F ;
Hemmi, H ;
Hochrein, H ;
Ampenberger, F ;
Kirschning, C ;
Akira, S ;
Lipford, G ;
Wagner, H ;
Bauer, S .
SCIENCE, 2004, 303 (5663) :1526-1529
[99]   A Toll-like receptor recognizes bacterial DNA [J].
Hemmi, H ;
Takeuchi, O ;
Kawai, T ;
Kaisho, T ;
Sato, S ;
Sanjo, H ;
Matsumoto, M ;
Hoshino, K ;
Wagner, H ;
Takeda, K ;
Akira, S .
NATURE, 2000, 408 (6813) :740-745
[100]   IgE-Mediated Enhancement of CD4+ T Cell Responses in Mice Requires Antigen Presentation by CD11c+ Cells and Not by B Cells [J].
Henningsson, Frida ;
Ding, Zhoujie ;
Dahlin, Joakim S. ;
Linkevicius, Marius ;
Carlsson, Fredrik ;
Gronvik, Kjell-Olov ;
Hallgren, Jenny ;
Heyman, Birgitta .
PLOS ONE, 2011, 6 (07)