Nucleosomes activate NF-kappaB in endothelial cells for induction of the proangiogenic cytokine IL-8.
Solid tumors often exhibit regions undergoing apoptosis and necrosis, also referred to as "aponecrosis", juxtaposed to sites of active angiogenesis. We explored whether nucleosomes resulting from aponecrosis induced the angiogenic factor IL-8 in vascular endothelial cells. Results indicate that nucleosomes induced IL-8. Nucleosomes increased IL-6 and IL-8 mRNA but not IL-10, TNF-alpha, VEGF or FGF-2 mRNA. Induction of IL-8 by nucleosomes in endothelial cells appeared to be the result of NF-kappaB/RelA transcription factor activation. The increased expression of IL-8 in vascular endothelial cells following nucleosome stimulation suggests that aponecrosis could play an important role in the promotion of tumor angiogenesis.
Tanner
Jerome E
JE
Laboratory of Anti-Nucleosome Antibody Therapeutics, Procyon Biopharma, Inc., Montreal, Quebec, Canada. jetanner@tantecbiosystems.com
D000970:Antineoplastic Agents / Q000378:metabolism; D002478:Cells, Cultured; D004730:Endothelium, Vascular / Q000502:physiology*; D016222:Fibroblast Growth Factor 2 / Q000235:genetics / Q000378:metabolism; D006801:Humans; D016753:Interleukin-10 / Q000235:genetics / Q000378:metabolism; D015850:Interleukin-6 / Q000235:genetics / Q000378:metabolism; D016209:Interleukin-8 / Q000235:genetics / Q000378:metabolism*; D016328:NF-kappa B / Q000378:metabolism*; D018919:Neovascularization, Physiologic; D009707:Nucleosomes / Q000378:metabolism*; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D014409:Tumor Necrosis Factor-alpha / Q000235:genetics / Q000378:metabolism; D014471:Umbilical Veins / Q000378:metabolism; D042461:Vascular Endothelial Growth Factor A / Q000235:genetics / Q000378:metabolism
D000970:Antineoplastic Agents; D015850:Interleukin-6; D016209:Interleukin-8; D016328:NF-kappa B; D009707:Nucleosomes; D012333:RNA, Messenger; D014409:Tumor Necrosis Factor-alpha; D042461:Vascular Endothelial Growth Factor A; D016222:Fibroblast Growth Factor 2; D016753:Interleukin-10