PMID: 16515014Mar 7, 2006Paper

Intracellular signaling mechanisms underlying the expression of pro-inflammatory mediators in airway diseases

Chang Gung Medical Journal
Chuen-Mao YangChiang-Wen Lee

Abstract

Several factors have been shown to trigger the pathogenesis of asthma and airway inflammation mechanisms. Elevated levels of pro-inflammatory cytokines including tumor necrosis factor-alpha and interleukin-1beta in the bronchoalveolar lavage fluid have been detected in asthmatic patients. Cytokines exert as potent stimuli in inflammatory responses through up-regulation of many gene expressions, including cytokines, chemokines, cytosolic phospholipase A2, cyclooxygenase, adhesion molecules and matrix metalloproteinases. The extent of these gene expressions is correlated with the severity of inflammation. However, the intracellular signaling mechanisms underlying the expression of target proteins regulated by these factors are elusive. The mechanisms underlying actions by cytokines may be integrated to the signaling networks that augment airway inflammation by recruiting leukocytes and leading to airway remodeling. Although cytokines have been reported to activate mitogen-activated protein kinases including p42/p44 and p38, and c-Jun N-terminal kinase, the relationship between the activation of these pathways and expression of inflammatory genes remains unknown. Moreover, many genes regulated by mitogen-activated protein kinases ...Continue Reading

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