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SPLUNC1 reduces the inflammatory response of nasopharyngeal carcinoma cells infected with the EB virus by inhibiting the TLR9/NF-κB pathway

  • Authors:
    • Chunlin Ou
    • Zhenqiang Sun
    • Han Zhang
    • Wei Xiong
    • Jian Ma
    • Ming Zhou
    • Jianhong Lu
    • Zhaoyang Zeng
    • Xiang Bo
    • Pan Chen
    • Guiyuan Li
    • Xiayu Li
    • Xiaoling Li

  • View Affiliations

  • Published online on: April 17, 2015     https://doi.org/10.3892/or.2015.3913
  • Pages: 2779-2788
Metrics: Total Views: 0 (Spandidos Publications: | PMC Statistics: )
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Abstract

Studies indicate that the natural immune-related protein short palate, lung, and nasal epithelium clone 1 (SPLUNC1) plays an antitumor role in nasopharyngeal epithelial tissue. However, the detailed mechanism of the tumor-suppressor effect of SPLUNC1 in the inflammatory microenvironment of Epstein-Barr virus (EBV)-associated nasopharyngeal carcinoma (NPC) remains elusive. The aim of the present study was to explore how SPLUNC1 reduces the inflammatory response of NPC cells infected with EBV by regulating the Toll-like receptor (TLR)9/NF-κB signaling pathway. As detected by immunohistochemistry and western blotting, SPLUNC1 protein expression exhibited low or negative expression in the NPC epithelial samples/cells, while it demonstrated positive expression in normal nasopharyngeal epithelial tissues/cells; this pattern of expression was the contrary to that of TLR9. The poorly differentiated HNE2 cell line had the highest efficiency of transfer of infection with EBV by ‘cell-to-cell’ contact method. The group of EBV-infected HNE2 cells showed significantly higher activation of the expression of TLR9/NF-κB signaling pathway-associated factors (TLR9, CD14, MyD88, IKK, P-IKβα, P-NF-κB and NF-κB). The levels of inflammatory cytokines IL-6, IL-8, IL-1β and TNF-α in the HNE2 cell group after EBV infection were higher than these levels in the uninfected cell group (P<0.05); Meanwhile, after EBV infection, the expression levels of TLR9/NF-κB pathway associated-protein and inflammatory cytokines IL-6, IL-8, IL-1β and TNF-α in the HNE2/SPLUNC1 cell group were lower than these levels in the HNE2/Vector cell group (P<0.05). After EBV-DNA direct transfection, cytokine mRNA expression levels of TLR9, IL-6, IL-8, IL-1β and TNF-α in the HNE2 cell group were significantly higher than these levels in the NP69 cell group (P<0.05). The expression levels of these cytokines in the HNE2/SPLUNC1 cell group were obviously lower than these levels in the HNE2/Vector cell group (P<0.05). These results suggest that EBV infection of NPC cells can activate the TLR9/NF-κB signaling pathway, promote the release of inflammatory cytokines and consequently enhance the inflammatory response, while SPLUNC1 can weaken the inflammatory response induced by EBV infection in NPC cells through the regulation of the TLR9/NF-κB signaling pathway and control of the tumor inflammatory microenvironment.
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June-2015
Volume 33 Issue 6

Print ISSN: 1021-335X
Online ISSN:1791-2431

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  • Impact Factor: 3.8
  • Ranked Oncology
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  • CiteScore: 8.5
  • CiteScore Rank: Q1: #74/404 Oncology
  • Source Normalized Impact per Paper (SNIP): 0.719
  • SCImago Journal Rank (SJR): 0.864
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Spandidos Publications style
Ou C, Sun Z, Zhang H, Xiong W, Ma J, Zhou M, Lu J, Zeng Z, Bo X, Chen P, Chen P, et al: SPLUNC1 reduces the inflammatory response of nasopharyngeal carcinoma cells infected with the EB virus by inhibiting the TLR9/NF-κB pathway. Oncol Rep 33: 2779-2788, 2015.
APA
Ou, C., Sun, Z., Zhang, H., Xiong, W., Ma, J., Zhou, M. ... Li, X. (2015). SPLUNC1 reduces the inflammatory response of nasopharyngeal carcinoma cells infected with the EB virus by inhibiting the TLR9/NF-κB pathway. Oncology Reports, 33, 2779-2788. https://doi.org/10.3892/or.2015.3913
MLA
Ou, C., Sun, Z., Zhang, H., Xiong, W., Ma, J., Zhou, M., Lu, J., Zeng, Z., Bo, X., Chen, P., Li, G., Li, X., Li, X."SPLUNC1 reduces the inflammatory response of nasopharyngeal carcinoma cells infected with the EB virus by inhibiting the TLR9/NF-κB pathway". Oncology Reports 33.6 (2015): 2779-2788.
Chicago
Ou, C., Sun, Z., Zhang, H., Xiong, W., Ma, J., Zhou, M., Lu, J., Zeng, Z., Bo, X., Chen, P., Li, G., Li, X., Li, X."SPLUNC1 reduces the inflammatory response of nasopharyngeal carcinoma cells infected with the EB virus by inhibiting the TLR9/NF-κB pathway". Oncology Reports 33, no. 6 (2015): 2779-2788. https://doi.org/10.3892/or.2015.3913