Synergistic up-regulation of CXCL10 by virus and IFN γ in human airway epithelial cells

Karen L. Oslund, Xu Zhou, Boram Lee, Lingxiang Zhu, Trang Duong, Robert Shih, Nicole Baumgarth, Li Yin Hung, Reen Wu, Yin Chen

Research output: Contribution to journalArticle

13 Scopus citations

Abstract

Airway epithelial cells are the first line of defense against viral infections and are instrumental in coordinating the inflammatory response. In this study, we demonstrate the synergistic stimulation of CXCL10 mRNA and protein, a key chemokine responsible for the early immune response to viral infection, following treatment of airway epithelial cells with IFN γ and influenza virus. The synergism also occurred when the cells were treated with IFN γ and a viral replication mimicker (dsRNA) both in vitro and in vivo. Despite the requirement of type I interferon (IFNAR) signaling in dsRNA-induced CXCL10, the synergism was independent of the IFNAR pathway since it wasn't affected by the addition of a neutralizing IFNAR antibody or the complete lack of IFNAR expression. Furthermore, the same synergistic effect was also observed when a CXCL10 promoter reporter was examined. Although the responsive promoter region contains both ISRE and NFκB sites, western blot analysis indicated that the combined treatment of IFN γ and dsRNA significantly augmented NFκB but not STAT1 activation as compared to the single treatment. Therefore, we conclude that IFN γ and dsRNA act in concert to potentiate CXCL10 expression in airway epithelial cells via an NFκB-dependent but IFNAR-STAT independent pathway and it is at least partly regulated at the transcriptional level.

Original languageEnglish (US)
Article numbere100978
JournalPLoS One
Volume9
Issue number7
DOIs
StatePublished - Jul 17 2014

ASJC Scopus subject areas

  • Agricultural and Biological Sciences(all)
  • Biochemistry, Genetics and Molecular Biology(all)
  • Medicine(all)

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    Oslund, K. L., Zhou, X., Lee, B., Zhu, L., Duong, T., Shih, R., Baumgarth, N., Hung, L. Y., Wu, R., & Chen, Y. (2014). Synergistic up-regulation of CXCL10 by virus and IFN γ in human airway epithelial cells. PLoS One, 9(7), [e100978]. https://doi.org/10.1371/journal.pone.0100978