Alpha- and betapapillomavirus E6/E7 genes differentially modulate pro-inflammatory gene expression.

Marco De Andrea; Michele Mondini; Barbara Azzimonti; Valentina Dell'Oste; Serena Germano; Giovanni Gaudino; Tiziana Musso; Santo Landolfo; Marisa Gariglio

doi:10.1016/j.virusres.2006.09.010

PubMed · 17079045

Alpha- and betapapillomavirus E6/E7 genes differentially modulate pro-inflammatory gene expression.

Marco De Andrea·Michele Mondini·Barbara Azzimonti·Valentina Dell'Oste·Serena Germano·Giovanni Gaudino·Tiziana Musso·Santo Landolfo·Marisa Gariglio

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Abstract

Keratinocytes, the target cell of human papillomavirus (HPV) infection, can produce numerous cytokines and pro-inflammatory molecules which are important for the generation of an effective immune response. How this biological response, which involves the tumor stroma, is affected by the HPV oncoproteins within the epithelial cell itself is not clear. Here it is shown that oncoproteins of different HPV genotypes (alpha- versus beta-HPV genus) alter the expression of pro-inflammatory molecules in early passage primary human keratinocytes and the immortalized cell line HaCaT. HPV5 E6/E7 oncoproteins significantly induced interleukin-8 (IL-8), monocyte chemoattractant protein-1 (MCP-1) and intercellular adhesion molecule-1 (ICAM-1) expression. By contrast, the same molecules were down-regulated or not modulated in HPV16 E6/E7 transduced keratinocytes. Interestingly, HPV38 oncoproteins expression resulted in a lower induction of pro-inflammatory molecules, resembling the behavior displayed by the mucosal carcinogenic HPV16. Finally, inducible nitric oxide synthase (iNOS) expression levels and nitric oxide (NO) production were induced at similar levels by all the HPV genotypes tested. These results further emphasize the different biological activities among HPV genotypes, and offer new insights into HPV-associated skin diseases.

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Alphapapillomavirus Betapapillomavirus Cell Line Cells, Cultured Chemokine CCL2 Human papillomavirus 16 Humans Intercellular Adhesion Molecule-1 Interleukin-8 Keratinocytes Nitric Oxide Nitric Oxide Synthase Oncogene Proteins, Viral Papillomavirus E7 Proteins Repressor Proteins Journal Article Research Support, Non-U.S. Gov't

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Marco De Andrea, Michele Mondini, Barbara Azzimonti, Valentina Dell'Oste, Serena Germano, Giovanni Gaudino, Tiziana Musso, Santo Landolfo, Marisa Gariglio. 2006-10-31. Alpha- and betapapillomavirus E6/E7 genes differentially modulate pro-inflammatory gene expression.. https://doi.org/10.1016/j.virusres.2006.09.010

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