1887

Abstract

Keratinocytes can be induced to produce cytokines by exogenous stimuli, such as UVB, and dysregulation of this production has been described in various skin diseases, including cancer. In this study, we compared the effect of UVB on the secretion of several cytokines involved in inflammation by human keratinocytes immortalized or not with human papillomavirus (HPV)16 or HPV38 at the mRNA and protein levels. We show that expression of the HPV E6/E7 oncoproteins influences not only the basal cytokine secretion profile of keratinocytes, but also its modulation upon UVB irradiation. In particular, UVB upregulates interleukin (IL)-6, IL-8 and transforming growth factor (TGF)- in HPV-immortalized cells to a higher extent than in control keratinocytes. Moreover, expression of other pro-inflammatory molecules such as S100A8/9 and interferon (IFN)- was downregulated in HPV-immortalized cells. These data support the functional similarity between HPV16 and 38, and suggest an active role of these viruses in modulation of the inflammatory process.

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2008-10-01
2024-03-28
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References

  1. Accardi R., Dong W., Smet A., Cui R., Hautefeuille A., Gabet A. S., Sylla B. S., Gissmann L., Hainaut P. other authors 2006; Skin human papillomavirus type 38 alters p53 functions by accumulation of ΔNp73. EMBO Rep 7:334–340 [CrossRef]
    [Google Scholar]
  2. Akgül B., Lemme W., Garcìa-Escudero R., Storey A., Pfister H. J. 2005; UV-B irradiation stimulates the promoter activity of the high-risk, cutaneous human papillomavirus 5 and 8 in primary keratinocytes. Arch Virol 150:145–151 [CrossRef]
    [Google Scholar]
  3. Akgül B., Cooke J. C., Storey A. 2006; HPV-associated skin disease. J Pathol 208:165–175 [CrossRef]
    [Google Scholar]
  4. Apte R. N., Krelin Y., Song Y., Dotan S., Recih E., Elkabets M., Carmi Y., Dvorkin T., White R. M. other authors 2006; Effects of micro-environment- and malignant cell-derived interleukin-1 in carcinogenesis, tumour invasiveness and tumour-host interactions. Eur J Cancer 42:751–759 [CrossRef]
    [Google Scholar]
  5. Barnard P., Payne E., McMillan N. A. J. 2000; The human papillomavirus E7 protein is able to inhibit the antiviral and anti-growth functions of interferon- α . Virology 277:411–419 [CrossRef]
    [Google Scholar]
  6. Buontempo P. J., Jubin R. G., Buotempo C. A., Wagner N. E., Reyes G. R., Baroudy B. M. 2006; Antiviral activity of transiently expressed IFN- κ is cell-associated. J Interferon Cytokine Res 26:40–52 [CrossRef]
    [Google Scholar]
  7. Caldeira S., Zehbe I., Accardi R., Malanchi I., Dong W., Giarrè M., de Villiers E. M., Filotico R., Boukamp P. other authors 2003; The E6 and E7 proteins of the cutaneous human papillomavirus type 38 display transforming properties. J Virol 77:2195–2206 [CrossRef]
    [Google Scholar]
  8. Coussens L. M., Hanahan D., Arbeit J. M. 1996; Genetic predisposition and parameters of malignant progression in K14–HPV16 transgenic mice. Am J Pathol 149:1899–1917
    [Google Scholar]
  9. De Andrea M., Mondini M., Azzimonti B., Dell'Oste V., Germano S., Gaudino G., Musso T., Landolfo S., Gariglio M. 2007; Alpha- and betapapillomavirus E6/E7 genes differentially modulate pro-inflammatory gene expression. Virus Res 124:220–225 [CrossRef]
    [Google Scholar]
  10. de Villiers E. M., Fauquet C., Broker T. R., Bernard H. U., zur Hausen H. 2004; Classification of papillomaviruses. Virology 324:17–27 [CrossRef]
    [Google Scholar]
  11. de Visser K. E., Eichten A., Coussens L. M. 2006; Paradoxical roles of the immune system during cancer development. Nat Rev Cancer 6:24–36 [CrossRef]
    [Google Scholar]
  12. Gabay C. 2006; Interleukin-6 and chronic inflammation. Arthritis Res Ther 8:Suppl. 2S3
    [Google Scholar]
  13. Gebhardt C., Nemeth J., Angel P., Hess J. 2006; S100A8 and S100A9 in inflammation and cancer. Biochem Pharmacol 72:1622–1631 [CrossRef]
    [Google Scholar]
  14. Jackson S., Harwood C., Thomas M., Banks L., Storey A. 2000; Role of Bak in UV-induced apoptosis in skin cancer and abrogation by HPV E6 proteins. Genes Dev 14:3065–3073 [CrossRef]
    [Google Scholar]
  15. Kishimoto T. 2006; Interleukin-6: discovery of a pleiotropic cytokine. Arthritis Res Ther 8:Suppl. 2S2
    [Google Scholar]
  16. Kondo S., Kono T., Sauder D. N., McKenzie R. C. 1993; IL-8 gene expression and production in human keratinocytes and their modulation by UVB. J Invest Dermatol 101:690–694 [CrossRef]
    [Google Scholar]
  17. Koromilas A. E., Li S., Matlashewski G. 2001; Control of interferon signaling in human papillomavirus infection. Cytokine Growth Factor Rev 12:157–170 [CrossRef]
    [Google Scholar]
  18. Kupper T. S., Chua A. O., Flood P., McGuire J., Gubler U. 1987; Interleukin 1 gene expression in cultured human keratinocytes is augmented by ultraviolet irradiation. J Clin Invest 80:430–436 [CrossRef]
    [Google Scholar]
  19. Li A. G., Lu S. L., Han G., Hoot K. E., Wang X. J. 2006; Role of TGF β in skin inflammation and carcinogenesis. Mol Carcinog 45:389–396 [CrossRef]
    [Google Scholar]
  20. Mueller M. M. 2006; Inflammation in epithelial skin tumours: old stories and new ideas. Eur J Cancer 42:735–744 [CrossRef]
    [Google Scholar]
  21. O'Brien P. M., Saveria Campo M. 2002; Evasion of host immunity directed by papillomavirus-encoded proteins. Virus Res 88:103–117 [CrossRef]
    [Google Scholar]
  22. Pear W. S., Nolan G. P., Scott M. L., Baltimore D. 1993; Production of high titre helper-free retroviruses by transient transfection. Proc Natl Acad Sci U S A 90:8392–8396 [CrossRef]
    [Google Scholar]
  23. Pfaffl M. W., Horgan G. W., Dempfle L. 2002; Relative expression software tool (rest©) for group-wise comparison and statistical analysis of relative expression results in real-time PCR. Nucleic Acids Res 30:e36 [CrossRef]
    [Google Scholar]
  24. Pfister H. 2003; Chapter 8: Human Papillomavirus and skin cancer. J Natl Cancer Inst Monogr 31:52–56
    [Google Scholar]
  25. Ronco L. V., Karpova A. Y., Vidal M., Howley P. M. 1998; Human papillomavirus 16 E6 oncoprotein binds to interferon regulatory factor-3 and inhibits its transcriptional activity. Genes Dev 12:2061–2072 [CrossRef]
    [Google Scholar]
  26. Ruhland A., De Villiers E. M. 2001; Opposite regulation of the HPV 20-URR and HPV 27-URR promoters by ultraviolet irradiation and cytokines. Int J Cancer 91:828–834 [CrossRef]
    [Google Scholar]
  27. Scarponi C., Nardelli B., Lafleur D. W., Moore P. A., Madonna S., De Pita O., Girolamoni G., Albanesi C. 2006; Analysis of IFN- κ expression in pathologic skin conditions: downregulation in psoriasis and atopic dermatitis. J Interferon Cytokine Res 26:133–140 [CrossRef]
    [Google Scholar]
  28. Simbulan-Rosenthal C. M., Velena A., Veldman T., Schlegel R., Rosenthal D. S. 2002; HPV-16 E6/7 immortalization sensitizes human keratinocytes to ultraviolet B by altering the pathway from caspase-8 to caspase-9-dependent apoptosis. J Biol Chem 277:24709–24716 [CrossRef]
    [Google Scholar]
  29. Smola-Hess S., de Silva U. S., Hadaschik D., Pfister H. 2001; Soluble IL-6 receptor activates the human papillomavirus type 18 long control region in SW756 cervical carcinoma cells in a STAT3-dependent manner. J Gen Virol 82:2335–2339
    [Google Scholar]
  30. Stanley M. 2006; Immune responses to human papillomavirus. Vaccine 24:S16–S22 [CrossRef]
    [Google Scholar]
  31. Strickland I., Rhodes L. E., Flanagran B. F., Friedmann P. 1997; TNF α and IL-8 are upregulated in the epidermis of normal human skin after UVB exposure: correlation with neutrophil accumulation and E-selectin expression. J Invest Dermatol 108:763–768 [CrossRef]
    [Google Scholar]
  32. Tindle R. W. 2002; Immune evasion in human papillomavirus-associated cervical cancer. Nat Rev Cancer 2:59–65 [CrossRef]
    [Google Scholar]
  33. Tugizov S., Berline J., Herrera R., Penaranda M. E., Nakagawa M., Palefsky J. 2005; Inhibition of human papillomavirus type 16 E7 phosphorylation by the S100 MRP-8/14 protein complex. J Virol 79:1099–1112 [CrossRef]
    [Google Scholar]
  34. van Kempen L. C. L., Ruiter D. J., van Muijen G. N. P., Coussens L. M. 2003; The tumour microenvironment: a critical determinant of neoplastic evolution. Eur J Cell Biol 82:539–548 [CrossRef]
    [Google Scholar]
  35. Woodworth C. D., Simpson S. 1993; Comparative lymphokine secretion by cultured normal human cervical keratinocytes, papillomavirus-immortalized and carcinoma cell lines. Am J Pathol 142:1544–1555
    [Google Scholar]
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