Login

Journal Image
Current Drug Targets
ISSN (Print): 1389-4501
ISSN (Online): 1873-5592
VOLUME: 7
ISSUE: 6
DOI: 10.2174/138945006777435353      Price:  $58









Targeting Mitogen-Activated Protein Kinases for Asthma

img
Author(s): Wei Duan and W.S. F. Wong
Pages 691-698 (8)
Abstract:
Allergic asthma is a chronic airway inflammatory disorder attributable to T-helper 2 cell responses together with other inflammatory cells such as mast cells, B cells and eosinophils, and pro-inflammatory cytokines and chemokines. Mitogen-activated protein kinase (MAPK) signaling cascades have been shown to be important in the differentiation, activation, proliferation, degranulation and migration of various immune cells, and airway smooth muscle and epithelial cells. In mammal, MAPK signaling modules are divided into at least 3 groups: extracellular signal-regulated kinase (ERK), p38 MAPK, and c-Jun NH2-terminal kinase (JNK). Each MAPK module plays a discrete yet complementary role in accentuating allergic airway inflammation. Cumulative evidence reveals potential anti-inflammatory activities of MAPK inhibitors in a variety of in vitro models of inflammation. Recently, the anti-inflammatory effects of MAPK kinase inhibitor (U0126), p38 MAPK inhibitors (SB239063 and respirable p38α MAPK antisense oligonucleotide) and JNK inhibitor (SP600125) have been demonstrated in in vivo animal models of asthma. Development of inhibitors targeting at MAPK could be an attractive strategy for the treatment of asthma.
Keywords:
extracellular signal-regulated protein kinase, p38 MAPK, c-Jun NH2-terminal kinase, cytokine, immune receptor, chemokine, animal models, airway smooth muscle cells, epithelial cells
Affiliation:
Department of Pharmacology,Faculty of Medicine, National University of Singapore, MD2 18 MedicalDrive, Singapore 117597.