Interleukin-5 (IL-5) plays a key role in the pathogenesis of bronchial asthma. Thrombin is a procoagulant factor that has been also reported to participate in the inflammatory response by stimulating the secretion of cytokines . Interaction of inflammatory cells with airway epithelial cells may also promote the secretion of cytokines. However, the role of Thrombin and cell-to-cell interaction in pathogenesis of allergic inflammation is unclear. In this study, we evaluated the role of thrombin and cell-to-cell interaction in the secretion of IL-5 from basophils. The human basophil cell line KU-812 was used in the assays. Thrombin and co-culture with alveolar epithelial cells significantly stimulated the secretion of IL-5 from KU-812 cells as compared to controls. Secretion of IL-5 was synergistically stimulated when KU-812 cells were incubated in the presence of both thrombin and alveolar epithelial cells. Co-culture of KU-812 cells with epithelial cells significantly increased the expression of tissue factor, an activator of coagulation activation, in a cell dose-dependent manner. Secretion of IL-5 from KU-812 basophils co-cultured with epithelial cells was significantly inhibited by LY294002, an inhibitor of phosphatidylinositol 3-kinase. These results suggest that thrombin and cell interaction with lung epithelial cells may augment the inflammatory response in allergic diseases by stimulating the secretion of IL-5 from basophils .
Yamaguchi A, Gabazza EC, Takei Y, Yano Y, Fujimoto H, D'Alessandro-Gabazza CN, Murakami E, Kobayashi T, Takagi T, Maruyama J, Suzuki K, Taguchi O.
Department of Pulmonary and Critical Care Medicine, Mie University Graduate School of Medicine, Edobashi 2-174, Tsu City, Mie Prefecture, Japan.Biochem Biophys Res Commun. 2008 Jan 18
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