title: Interferon-gamma enhances rhinovirus-induced RANTES secretion by airway epithelial cells.
abstract: Respiratory viruses, including rhinoviruses, infect respiratory epithelium and induce a variety of cytokines and chemokines that can initiate an inflammatory response. Cytokines, such as interferon (IFN)-gamma and tumor necrosis factor (TNF)-alpha, could enhance epithelial cell activation by inducing virus receptors. To test this hypothesis, effects of IFN-gamma or TNF-alpha on expression of intercellular adhesion molecule (ICAM)-1, rhinovirus binding, and virus-induced chemokine secretion on A549 and human bronchial epithelial cells (HBEC) were determined. The results varied with the type of cell. IFN-gamma was a stronger inducer of ICAM-1 and viral binding on HBEC, whereas TNF-alpha had greater effects on A549 cells. In addition, IFN-gamma, but not TNF-alpha, synergistically enhanced regulated on activation, normal T cells expressed and secreted (RANTES) mRNA expression and protein secretion induced by RV16 or RV49. To determine whether IFN-gamma could enhance RANTES secretion independent of effects on ICAM-1 and RV binding, HBEC were transfected with RV16 RNA in the presence or absence of IFN-gamma. RV16 RNA alone stimulated RANTES secretion, and this effect was enhanced by IFN-gamma. These results demonstrate that IFN-gamma can enhance rhinovirus-induced RANTES secretion by increasing viral binding, and through a second receptor-independent pathway. These findings suggest that IFN-gamma, by upregulating RANTES secretion, could be an important regulator of the initial immune response to rhinovirus infections.
authors.affiliation: Department of Medicine, University of Wisconsin-Madison, Madison, Wisconsin, USA.
authors.forename: Shinichi
authors.initials: S
authors.lastname: Konno
authors.forename: Kristine A
authors.initials: KA
authors.lastname: Grindle
authors.forename: Wai-Ming
authors.initials: WM
authors.lastname: Lee
authors.forename: Mary K
authors.initials: MK
authors.lastname: Schroth
authors.forename: Anne G
authors.initials: AG
authors.lastname: Mosser
authors.forename: Rebecca A
authors.initials: RA
authors.lastname: Brockman-Schneider
authors.forename: William W
authors.initials: WW
authors.lastname: Busse
authors.forename: James E
authors.initials: JE
authors.lastname: Gern
mesh_terms: D000998:Antiviral Agents / Q000494:pharmacology*; D002478:Cells, Cultured; D018946:Chemokine CCL5 / Q000378:metabolism*; D004357:Drug Synergism; D004847:Epithelial Cells / Q000166:cytology / Q000187:drug effects / Q000378:metabolism / Q000821:virology; D006801:Humans; D018799:Intercellular Adhesion Molecule-1 / Q000096:biosynthesis; D007371:Interferon-gamma / Q000494:pharmacology*; D011485:Protein Binding / Q000187:drug effects; D012330:RNA, Double-Stranded / Q000494:pharmacology; D012367:RNA, Viral / Q000008:administration & dosage / Q000378:metabolism; D020545:Respiratory Mucosa / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism* / Q000821:virology; D012229:Rhinovirus / Q000187:drug effects / Q000378:metabolism*; D014162:Transfection; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology; D014779:Virus Replication / Q000187:drug effects
chemical_list: D000998:Antiviral Agents; D018946:Chemokine CCL5; D012330:RNA, Double-Stranded; D012367:RNA, Viral; D014409:Tumor Necrosis Factor-alpha; D018799:Intercellular Adhesion Molecule-1; D007371:Interferon-gamma