title: Upregulation of interleukin-4 receptor by interferon-gamma: enhanced interleukin-4-induced eotaxin-3 production in airway epithelium.
abstract: Airway epithelial cells produce a number of chemokines, including eotaxins. Among the three known eotaxins, T helper (Th) type 2 cytokines have been observed to induce the expression of eotaxin-3 mRNA. This study investigated the effect of interferon (IFN)-gamma, a Th1 cytokine, on Th2 cytokine-induced eotaxin-3 production in a bronchial epithelial cell line, BEAS-2B. BEAS-2B cells produced eotaxin-3 after stimulation with the Th2 cytokines interleukin (IL)-13 and IL-4. When BEAS-2B cells were cultured with varying concentrations of IFN-gamma for 24 h, dose-dependent inhibition of Th2 cytokine-induced eotaxin-3 mRNA expression and protein production was observed. This was associated with downregulation of signal transducer and activator of transcription 6 activation. On the other hand, 2-d pretreatment of BEAS-2B cells with IFN-gamma dose-dependently enhanced Th2 cytokine-induced eotaxin-3 mRNA expression and production. IFN-gamma also increased the mRNA expression and protein production of IL-4 receptor (R) alpha in a time- and dose-dependent manner. In addition, IL-2Rgamma, a component of the type 1 IL-4R, was also upregulated by IFN-gamma. These results indicate that IFN-gamma has opposite effects on Th2 cytokine-induced eotaxin-3 production in BEAS-2B cells, depending on the length of exposure. Because high levels of IFN-gamma are produced during viral infection, airway viral infection may affect allergic airway inflammation in vivo by modulation of eotaxin-3 production.
authors.affiliation: Department of Pediatrics, School of Medicine, Saga University, 5-1-1 Nabeshima, Saga-City, Saga 849-8501, Japan. yamamot6@med.saga-u.ac.jp
authors.forename: Shuichi
authors.initials: S
authors.lastname: Yamamoto
authors.forename: Ikuko
authors.initials: I
authors.lastname: Kobayashi
authors.forename: Kohsuke
authors.initials: K
authors.lastname: Tsuji
authors.forename: Natsuko
authors.initials: N
authors.lastname: Nishi
authors.forename: Eriko
authors.initials: E
authors.lastname: Muro
authors.forename: Michiko
authors.initials: M
authors.lastname: Miyazaki
authors.forename: Masafumi
authors.initials: M
authors.lastname: Zaitsu
authors.forename: Shigeyasu
authors.initials: S
authors.lastname: Inada
authors.forename: Tomohiro
authors.initials: T
authors.lastname: Ichimaru
authors.forename: Yuhei
authors.initials: Y
authors.lastname: Hamasaki
mesh_terms: D000970:Antineoplastic Agents / Q000494:pharmacology*; D001980:Bronchi / Q000166:cytology / Q000378:metabolism; D000075906:Chemokine CCL26; D019742:Chemokines, CC / Q000235:genetics / Q000378:metabolism*; D004804:Eosinophils / Q000378:metabolism; D004847:Epithelial Cells / Q000166:cytology / Q000378:metabolism*; D006801:Humans; D007371:Interferon-gamma / Q000494:pharmacology*; D018793:Interleukin-13 / Q000494:pharmacology; D015847:Interleukin-4 / Q000494:pharmacology*; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D019948:Receptors, Interleukin-4 / Q000378:metabolism*; D018417:Th1 Cells / Q000378:metabolism; D018418:Th2 Cells / Q000378:metabolism; D015854:Up-Regulation
chemical_list: D000970:Antineoplastic Agents; C120429:CCL26 protein, human; D000075906:Chemokine CCL26; D019742:Chemokines, CC; D018793:Interleukin-13; D012333:RNA, Messenger; D019948:Receptors, Interleukin-4; D015847:Interleukin-4; D007371:Interferon-gamma