title: Role of thrombin in interleukin-5 expression from basophils.
abstract: 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.
authors.affiliation: Department of Pulmonary and Critical Care Medicine, Mie University Graduate School of Medicine, Edobashi 2-174, Tsu City, Mie Prefecture, Japan.
authors.forename: Aiko
authors.initials: A
authors.lastname: Yamaguchi
authors.forename: Esteban C
authors.initials: EC
authors.lastname: Gabazza
authors.forename: Yoshiyuki
authors.initials: Y
authors.lastname: Takei
authors.forename: Yutaka
authors.initials: Y
authors.lastname: Yano
authors.forename: Hajime
authors.initials: H
authors.lastname: Fujimoto
authors.forename: Corina N
authors.initials: CN
authors.lastname: D'Alessandro-Gabazza
authors.forename: Eiko
authors.initials: E
authors.lastname: Murakami
authors.forename: Tetsu
authors.initials: T
authors.lastname: Kobayashi
authors.forename: Takehiro
authors.initials: T
authors.lastname: Takagi
authors.forename: Junko
authors.initials: J
authors.lastname: Maruyama
authors.forename: Koji
authors.initials: K
authors.lastname: Suzuki
authors.forename: Osamu
authors.initials: O
authors.lastname: Taguchi
mesh_terms: D001491:Basophils / Q000187:drug effects* / Q000378:metabolism*; D002460:Cell Line; D018920:Coculture Techniques; D004847:Epithelial Cells / Q000187:drug effects / Q000378:metabolism; D006801:Humans; D015848:Interleukin-5 / Q000378:metabolism*; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism; D000081082:Phosphoinositide-3 Kinase Inhibitors; D047428:Protein Kinase Inhibitors / Q000494:pharmacology; D018179:Receptors, Thrombin / Q000378:metabolism; D013917:Thrombin / Q000494:pharmacology*
chemical_list: D015848:Interleukin-5; D019869:Phosphatidylinositol 3-Kinases; D000081082:Phosphoinositide-3 Kinase Inhibitors; D047428:Protein Kinase Inhibitors; D018179:Receptors, Thrombin; D013917:Thrombin