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Autocrine regulation of interleukin‐8 by interleukin‐1α in respiratory syncytial virus‐infected pulmonary epithelial cells in vitro
Author(s) -
Janak A. Patel,
Zili Jiang,
Natsuki Nakajima,
Masaru Kunimoto
Publication year - 1998
Publication title -
immunology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.297
H-Index - 133
eISSN - 1365-2567
pISSN - 0019-2805
DOI - 10.1046/j.1365-2567.1998.00640.x
Subject(s) - a549 cell , biology , tumor necrosis factor alpha , interleukin , microbiology and biotechnology , in vitro , incubation , virus , cell culture , cytokine , neutralizing antibody , virology , immunology , biochemistry , genetics
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‐1α, IL‐1‐β and tumour necrosis factor‐α (TNF‐α), 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‐1α, IL‐1β and TNF‐α showed that IL‐1α was the predominant soluble mediator that enhanced the mRNA expression and synthesis of IL‐8. IL‐1β and TNF‐α 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‐1α. In clinical settings, inhibitors of IL‐1α may be useful in suppressing inflammation due toIL‐1α as well as IL‐8.