title: Autocrine regulation of interleukin-8 by interleukin-1alpha in respiratory syncytial virus-infected pulmonary epithelial cells in vitro.
abstract: Respiratory epithelial cells infected with respiratory syncytial virus (RSV) produce interleukin-8 (IL-8); however, the mechanisms of RSV-induced regulation of IL-8 are poorly understood. In the present study, the regulation of IL-8 by RSV was evaluated using pulmonary type II-like epithelials (A549). Live purified RSV (pRSV) induced a significant increase in IL-8 after 8 hr of exposure, while conditioned supernatants from pRSV-infected A549 cells (cRSV) induced IL-8 production in fresh A549 cultures within 4 hr of infection. Furthermore, cRSV that had been rendered non-infectious by ultraviolet-irradiation (UV-cRSV) or ribavirin treatment also induced an increased production of IL-8 in fresh A549 cells, suggesting that RSV induced the synthesis of a soluble mediator(s) which in turn enhanced the synthesis of IL-8. We have previously shown that RSV-infected A549 cells produce IL-1alpha, IL-1-beta and tumour necrosis factor-alpha (TNF-alpha), which by themselves are known to induce the synthesis of IL-8. Preincubation of UV-cRSV or simultaneous incubation of pRSV with recombinant IL-1 receptor antagonist almost completely blocked (95-98%) the production of IL-8 by A549 cells. Furthermore, incubation with neutralizing antibodies against IL-1alpha, IL-1beta and TNF-alpha showed that IL-1alpha was the predominant soluble mediator that enhanced the mRNA expression and synthesis of IL-8. IL-1beta and TNF-alpha induced the synthesis of IL-8 at 24 hr, but partially inhibited the synthesis at 48 hr. In summary, these experiments provide direct evidence for an autocrine mechanism of enhanced IL-8 production in RSV-infected epithelial cells that is primarily mediated by IL-1alpha. In clinical settings, inhibitors of IL-1alpha may be useful in suppressing inflammation due to IL-1alpha as well as IL-8.
authors.affiliation: Division of Pediatric Infectious Diseases, Department of Pediatrics, Children's Hospital at University of Texas Medical Branch, Galveston, TX, USA.
authors.forename: J A
authors.initials: JA
authors.lastname: Patel
authors.forename: Z
authors.initials: Z
authors.lastname: Jiang
authors.forename: N
authors.initials: N
authors.lastname: Nakajima
authors.forename: M
authors.initials: M
authors.lastname: Kunimoto
mesh_terms: D000911:Antibodies, Monoclonal / Q000494:pharmacology; D019898:Autocrine Communication / Q000502:physiology*; D002460:Cell Line; D004848:Epithelium / Q000276:immunology; D006801:Humans; D007375:Interleukin-1 / Q000276:immunology / Q000494:pharmacology*; D016209:Interleukin-8 / Q000032:analysis / Q000235:genetics / Q000378:metabolism*; D008168:Lung / Q000276:immunology* / Q000821:virology*; D020033:Protein Isoforms; D012333:RNA, Messenger / Q000032:analysis; D018357:Respiratory Syncytial Virus Infections / Q000276:immunology*; D014409:Tumor Necrosis Factor-alpha / Q000276:immunology; D014776:Virus Cultivation
chemical_list: D000911:Antibodies, Monoclonal; D007375:Interleukin-1; D016209:Interleukin-8; D020033:Protein Isoforms; D012333:RNA, Messenger; D014409:Tumor Necrosis Factor-alpha