Constitutive release of IL6 by human papillomavirus type 16 (HPV16)-harboring keratinocytes: a mechanism augmenting the NK-cell-mediated lysis of HPV-bearing neoplastic cells.
In the present study we demonstrate that the cultured human keratinocyte cell line (SK-v cells) harboring and expressing integrated human papillomavirus type 16 (HPV16) DNA sequences constitutively releases IL6, which is known as a pleiotropic immunoregulatory cytokine of potential antitumor properties. The presence of IL6 activity in SK-v cell-conditioned media (SK-v CM) was demonstrated by tritiated thymidine incorporation into IL6-dependent B9 murine plasmacytoma cells. The effect on B9 cells was specific since it could be inhibited by anti-IL6 neutralizing antibodies but not by a normal control serum. IL6 did not affect SK-v cell growth; however, it significantly augmented NK cell activity of human peripheral blood lymphocytes against both K562 erytholeukemic and SK-v cells as assessed by 51Cr release assay. SK-v CM displayed NK cell-augmenting activity that copurified with IL6 activity in both size exclusion and anion-exchange HPLC. Furthermore, SK-v cell-derived NK cell stimulatory activity could be neutralized with anti-IL6 antibodies. These results suggest that HPV-harboring neoplastic cells can release IL6 which may indirectly mediate tumor death by augmentation of NK cell activity.
Malejczyk
J
J
Department of Histology and Embryology, Warsaw Medical School, Poland.
Malejczyk
M
M
Urbanski
A
A
Köck
A
A
Jablonska
S
S
Orth
G
G
Luger
T A
TA
D003602:Cytotoxicity, Immunologic; D006801:Humans; D015850:Interleukin-6 / Q000378:metabolism* / Q000494:pharmacology; D015603:Keratinocytes / Q000378:metabolism / Q000382:microbiology*; D007694:Killer Cells, Natural / Q000276:immunology*; D009369:Neoplasms / Q000382:microbiology* / Q000473:pathology; D027383:Papillomaviridae / Q000235:genetics*
D015850:Interleukin-6