Synergistic up-regulation of CXCL10 by virus and IFN γ in human airway epithelial cells.
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 infe...
| Main Authors: | , , , , , , , , , |
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| Format: | Article |
| Language: | English |
| Published: |
Public Library of Science (PLoS)
2014-01-01
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| Series: | PLoS ONE |
| Online Access: | http://europepmc.org/articles/PMC4102466?pdf=render |
| _version_ | 1818948177387061248 |
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| author | Karen L Oslund Xu Zhou Boram Lee Lingxiang Zhu Trang Duong Robert Shih Nicole Baumgarth Li-Yin Hung Reen Wu Yin Chen |
| author_facet | Karen L Oslund Xu Zhou Boram Lee Lingxiang Zhu Trang Duong Robert Shih Nicole Baumgarth Li-Yin Hung Reen Wu Yin Chen |
| author_sort | Karen L Oslund |
| collection | DOAJ |
| description | 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. |
| first_indexed | 2024-12-20T08:42:39Z |
| format | Article |
| id | doaj.art-0e91005d13a941159c36d5965d06f883 |
| institution | Directory Open Access Journal |
| issn | 1932-6203 |
| language | English |
| last_indexed | 2024-12-20T08:42:39Z |
| publishDate | 2014-01-01 |
| publisher | Public Library of Science (PLoS) |
| record_format | Article |
| series | PLoS ONE |
| spelling | doaj.art-0e91005d13a941159c36d5965d06f8832022-12-21T19:46:20ZengPublic Library of Science (PLoS)PLoS ONE1932-62032014-01-0197e10097810.1371/journal.pone.0100978Synergistic up-regulation of CXCL10 by virus and IFN γ in human airway epithelial cells.Karen L OslundXu ZhouBoram LeeLingxiang ZhuTrang DuongRobert ShihNicole BaumgarthLi-Yin HungReen WuYin ChenAirway 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.http://europepmc.org/articles/PMC4102466?pdf=render |
| spellingShingle | Karen L Oslund Xu Zhou Boram Lee Lingxiang Zhu Trang Duong Robert Shih Nicole Baumgarth Li-Yin Hung Reen Wu Yin Chen Synergistic up-regulation of CXCL10 by virus and IFN γ in human airway epithelial cells. PLoS ONE |
| title | Synergistic up-regulation of CXCL10 by virus and IFN γ in human airway epithelial cells. |
| title_full | Synergistic up-regulation of CXCL10 by virus and IFN γ in human airway epithelial cells. |
| title_fullStr | Synergistic up-regulation of CXCL10 by virus and IFN γ in human airway epithelial cells. |
| title_full_unstemmed | Synergistic up-regulation of CXCL10 by virus and IFN γ in human airway epithelial cells. |
| title_short | Synergistic up-regulation of CXCL10 by virus and IFN γ in human airway epithelial cells. |
| title_sort | synergistic up regulation of cxcl10 by virus and ifn γ in human airway epithelial cells |
| url | http://europepmc.org/articles/PMC4102466?pdf=render |
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