Novel Strategies for the Treatment of Asthma

被引:12
作者
Takizawa, Hajime [1 ]
机构
[1] Teikyo Univ, Sch Med, Dept Internal Med 4, Takatsu Ku, 3-8-3 Mizonokuchi, Kawasaki, Kanagawa 2138507, Japan
关键词
Asthma; mucosal epithelial cell; myofibroblast; smooth muscle cell; cytokines; chemokines; growth factor; signal transduction; transcription factor; statins;
D O I
10.2174/187221307779815101
中图分类号
R9 [药学];
学科分类号
1007 ;
摘要
It is now clear that airway inflammatory processes characterized by eosinophils and Th2 lymphocytes are pivotal as the pathological features of asthma. Standard inhaled corticosteroids markedly suppress such inflammatory changes, resulting in clinical beneficial effects. However, it is also notified that airway wall remodeling including goblet cell hyperplasia, sub-epithelial collagen deposits, increased capillary networks and smooth muscle hypertrophy occur as a chronic consequence of this disorder even by the recommended strategies with steroid treatment. These pathologic changes play an important role in the increased airway obstruction and hyperresponsiveness, and eventually in the development of irreversible respiratory failure. Recent studies have elucidated that myofibroblasts and smooth muscle as well as mucosal epithelial cells play a vital role in these processes. Agents regulating proliferation, differentiation and activity of these cells, especially of low-molecular weight compounds, attract attention. Studies on molecular mechanisms of above processes, have led the development and patents of potential drugs including inhibitors of NF kappaB, statins, macrolides and phosphodiesterase-4 inhibitors.
引用
收藏
页码:13 / 19
页数:7
相关论文
共 63 条
[1]  
Alonso-Alija C, 2006, Patent No. [US20060046999, 20060046999]
[2]   Making sense of latent TGFβ activation [J].
Annes, JP ;
Munger, JS ;
Rifkin, DB .
JOURNAL OF CELL SCIENCE, 2003, 116 (02) :217-224
[3]  
Balasubramanian G., 2006, [No title captured], Patent No. [WO06011024A3, 06011024]
[4]   Tryptase-stimulated human airway smooth muscle cells induce cytokine synthesis and mast cell chemotaxis [J].
Berger, P ;
Girodet, PO ;
Begueret, H ;
Ousova, O ;
Perng, DW ;
Marthan, R ;
Walls, AF ;
de Lara, JMT .
FASEB JOURNAL, 2003, 17 (12) :2139-+
[5]   Evidence of a role of tumor necrosis factor α in refractory asthma [J].
Berry, MA ;
Hargadon, B ;
Shelley, M ;
Parker, D ;
Shaw, DE ;
Green, RH ;
Bradding, P ;
Brightling, CE ;
Wardlaw, AJ ;
Pavord, ID .
NEW ENGLAND JOURNAL OF MEDICINE, 2006, 354 (07) :697-708
[6]   Airway smooth muscle - its relationship to the extracellular matrix [J].
Black, JL ;
Burgess, JK ;
Johnson, PRA .
RESPIRATORY PHYSIOLOGY & NEUROBIOLOGY, 2003, 137 (2-3) :339-346
[7]   Factors controlling smooth muscle proliferation and airway remodelling [J].
Black, Judith L. ;
Johnson, Peter R. A. .
CURRENT OPINION IN ALLERGY AND CLINICAL IMMUNOLOGY, 2002, 2 (01) :47-51
[8]  
BLAKE FJ, 2006, Patent No. 20060040972
[9]   MYOFIBROBLASTS AND SUBEPITHELIAL FIBROSIS IN BRONCHIAL-ASTHMA [J].
BREWSTER, CEP ;
HOWARTH, PH ;
DJUKANOVIC, R ;
WILSON, J ;
HOLGATE, ST ;
ROCHE, WR .
AMERICAN JOURNAL OF RESPIRATORY CELL AND MOLECULAR BIOLOGY, 1990, 3 (05) :507-511
[10]   Mast-cell infiltration of airway smooth muscle in asthma [J].
Brightling, CE ;
Bradding, P ;
Symon, FA ;
Holgate, ST ;
Wardlaw, AJ ;
Pavord, ID .
NEW ENGLAND JOURNAL OF MEDICINE, 2002, 346 (22) :1699-1705