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Published ahead of print on July 1, 2004, doi:10.1165/rcmb.2004-0128OC
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American Journal of Respiratory Cell and Molecular Biology. Vol. 31, pp. 456-462, 2004
© 2004 American Thoracic Society
DOI: 10.1165/rcmb.2004-0128OC

Upregulation of Interleukin-4 Receptor by Interferon-{gamma}

Enhanced Interleukin-4–Induced Eotaxin-3 Production in Airway Epithelium

Shuichi Yamamoto, Ikuko Kobayashi, Kohsuke Tsuji, Natsuko Nishi, Eriko Muro, Michiko Miyazaki, Masafumi Zaitsu, Shigeyasu Inada, Tomohiro Ichimaru and Yuhei Hamasaki

Department of Pediatrics, School of Medicine, Saga University, Saga, Japan

Address correspondence to: Shuichi Yamamoto, M.D., Department of Pediatrics, School of Medicine, Saga University, 5-1-1 Nabeshima, Saga-City, Saga 849-8501, Japan. E-mail: yamamot6{at}med.saga-u.ac.jp

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-2R{gamma}, 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.

Abbreviations: actinomycin D, ACD • cycloheximide, CHX • enzyme-linked immunosorbent assay, ELISA • fetal bovine serum, FBS • common {gamma} chain of interleukin-2 receptor, {gamma}C • interferon, IFN • interleukin, IL • IL-4 receptor, IL-4R • mitogen-activated protein kinase, MAPK • nuclear factor-{kappa}B, NF-{kappa}B • phosphate-buffered saline, PBS • phosphorylated signal transducer and activator of transcription, p-STAT • reverse transcription–polymerase chain reaction, RT-PCR • rhinovirus, RV • signal transducer and activator of transcription, STAT • T helper type, Th • tumor necrosis factor, TNF




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