Intracellular signaling mechanisms underlying the expression of pro-inflammatory mediators in airway diseases.
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 are dependent on NF-kappaB for transcription. NF-kappaB has also been shown to be involved in target protein expression at the transcriptional level in various cell types. We review the mechanisms underlying the intracellular signaling involved in several target protein expressions induced by cytokines in airway resident cells.


CONCLUSIONS
Increased understanding of signal transduction mechanisms underlying target protein gene expression will create opportunities for the development of anti-inflammation therapeutic strategies.
Yang
Chuen-Mao
CM
Graduate Institute of Natural Products, Chang Gung University, Taoyuan. chuen-mao@mail.cgu.edu.tw
Hsieh
Hsi-Lung
HL
Lee
Chiang-Wen
CW
D001249:Asthma / Q000209:etiology*; D051546:Cyclooxygenase 2 / Q000502:physiology; D015232:Dinoprostone / Q000502:physiology; D006801:Humans; D018836:Inflammation Mediators / Q000502:physiology*; D020780:Matrix Metalloproteinase 9 / Q000502:physiology; D010741:Phospholipases A / Q000502:physiology; D054467:Phospholipases A2; D015398:Signal Transduction / Q000502:physiology*; D019010:Vascular Cell Adhesion Molecule-1 / Q000502:physiology
D018836:Inflammation Mediators; D019010:Vascular Cell Adhesion Molecule-1; D051546:Cyclooxygenase 2; D010741:Phospholipases A; D054467:Phospholipases A2; D020780:Matrix Metalloproteinase 9; D015232:Dinoprostone