Abstract:
:We have proposed that chronic infection of keratinocytes by HPV modifies the expression of potentially important cytokines by interfering with the NF-kappaB signal pathway. We evaluated the constitutive and IL-1beta-induced expression of GM-CSF and TNF-alpha and the expression/activity of NF-kappaB in HPV+ and HPV- cell lines. Despite the enhanced expression of the functional components of the NF-kappaB signaling pathway in HPV+ cell lines by a mechanism implicating the HPV oncoprotein E6, the constitutive activity of NF-kappaB and the expression of GM-CSF/TNF-alpha were significantly reduced relative to the HPV- cell line and normal keratinocytes. In contrast, we observed a superactivation of NF-kappaB activity after IL-1beta stimulation, a strong and transient induction of GM-CSF/TNF-alpha mRNA, but undetectable levels of secreted proteins in HPV+ cell lines. Our data demonstrate that E6 modulates the NF-kappaB signaling pathway and suggest that other HPV proteins also interfere with GM-CSF/TNF-alpha expression by transcriptional and/or posttranscriptional mechanisms.
journal_name
Virologyjournal_title
Virologyauthors
Havard L,Delvenne P,Fraré P,Boniver J,Giannini SLdoi
10.1006/viro.2002.1468subject
Has Abstractpub_date
2002-07-05 00:00:00pages
271-85issue
2eissn
0042-6822issn
1096-0341pii
S0042682202914686journal_volume
298pub_type
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