Helicobacter pylori prevents proliferative stage of angiogenesis in vitro: role of cytokines.
Inhibition of angiogenesis may explain the delayed ulcer healing following Helicobacter pylori infection. We have previously demonstrated that H. pylori can inhibit endothelial cell proliferation. Some cytokines possess antiangiogenic properties. This study assessed a role for IL-6, IL-8, and TNF-a in H. pylori-induced endothelial cytostasis. First, 30 microl of H. pylori was coincubated with microvascular endothelial cells in the presence or absence of monoclonal antibodies to IL-6, IL-8, and TNF-a for 24, 48, 72, or 96 hr. Dual labeling with propidium iodide and Hoescht 33342 distinguished between necrosis, and apoptosis and allowed viable cell numbers to be determined. H. pylori decreased cell viability after 72 and 96 hr (P < 0.02). Neither necrosis nor apoptosis was observed. Monoclonal antibodies to IL-6 and IL-8 did not reverse cytostasis. However, significant MVEC proliferation was observed in the presence of the TNF-a monoclonal antibody. In conclusion, H. pylori induces cytokine up-regulation as part of its pathophysiological mechanism, which could prove detrimental to ulcer healing through an inhibitory effect on angiogenesis.
Division of Clinical Sciences (S), Royal Hallamshire Hospital, Sheffield, UK.
Lesley
L
Jenkinson
Karna Dev
KD
Bardhan
John
J
Atherton
Neena
N
Kalia
D001562:Benzimidazoles; D002455:Cell Division / Q000502:physiology; D004730:Endothelium, Vascular / Q000166:cytology; D016480:Helicobacter pylori / Q000502:physiology*; D006801:Humans; D066298:In Vitro Techniques; D015850:Interleukin-6 / Q000502:physiology*; D016209:Interleukin-8 / Q000502:physiology*; D018919:Neovascularization, Physiologic / Q000502:physiology*; D011419:Propidium; D014409:Tumor Necrosis Factor-alpha / Q000502:physiology*; D015854:Up-Regulation
D001562:Benzimidazoles; D015850:Interleukin-6; D016209:Interleukin-8; D014409:Tumor Necrosis Factor-alpha; D011419:Propidium; C017807:bisbenzimide ethoxide trihydrochloride