Expression Of Protease-activated Receptors (PARs) And Its Stimulation On Chemokine Release In A549 Cells

Asthma is a disease characterized by reversible airway obstruction, bronchial hyper-reactivity, and inflammation, and is associated with a predisposition toward atopy. Allergy to a variety of allergens has been described. The precise relationship between allergy and asthma is incompletely understood. But the respiratory epithelium is important because it is the first tissue to meet inhaled allergen and is capable of releasing some mediators and cytokines known to be associated with both diseases. For example, respiratory epithelial cells synthesize a variety of proinflammatory cytokines and chemokines such as IL-1, IL-6, GM-CSF, IL-8, macrophage-inflammatory protein, eotaxin, and RANTES, all of which regulate inflammation through their effects on cell recruitment, activation, and survival.The importance of serine proteinases in the development of airway diseases has been emphasized in recent years. Of particular importance is that the potential role of tryptase, thrombin and elastase in the development of asthma, in which these serine proteinases were not only been over-secreted, but also found to play a role in induction of cytokine hypersecretion in airways. However, the potential mechanism, through which these serine proteinases carry out their actions in respiratory tract, remains unclear. Since increased level of IL-8 and MCP-1 in the airways reported to be closely correlated to asthma, we investigated the effect of tryptase, thrombin, trypsin, and elastase on IL-8 and MCP-1 secretion and gene expression in A549 cells, a type II alveolar epithelial cell line from human adenocarcinoma, in the present study.In recent years, Protease-activated receptors (PARs) have been identified as receptors for serine proteinases. PARs are a subfamily of G-protein-coupled, seven-transmembrane domain receptors, which are cleaved within the aminoterminal exodomain by certain serine...