Apoptosis, inflammatory bowel disease and carcinogenesis: overview of international and Greek experiences.
Apoptosis is critical for organ development, tissue homeostasis, the elimination of abnormal cells and the maintenance of immune homeostasis by variable regulatory mechanisms. The death of T lymphocytes following their activation involves a series of proteases (caspases), which comprise the central executioners of apoptosis. Abnormal regulation of apoptosis results in disease. T-cell resistance against apoptosis contributes to inappropriate T-cell accumulation and the perpetuation of the chronic inflammatory process in inflammatory bowel disease with potential tumourigenic effect. The use of antitumour necrosis factor-alpha, anti-interleukin-6R and anti-interleukin-12 antibodies suppresses colitis activity by induction of T-cell apoptosis, thereby having important implications for the design of effective therapeutic strategies in inflammatory bowel diseases. Contrary to international data, the incidence of cancer in Greek patients with inflammatory bowel disease appears to be low. A balance between cell proliferation (Ki-67 overexpression) and apoptosis (Bax protein overexpression) may partly explain the low incidence of cancer development in Greek inflammatory bowel disease patients.
Kountouras
Jannis
J
Department of Medicine, Second Medical Clinic, Aristotle University of Thessaloniki, Ippokration Hospital, Greece. jannis@med.auth.gr
Kouklakis
Georgios
G
Zavos
Christos
C
Chatzopoulos
Dimitrios
D
Moschos
John
J
Molyvas
Epaminodas
E
Zavos
Nikolaos
N
D000818:Animals; D000906:Antibodies / Q000276:immunology / Q000627:therapeutic use; D017209:Apoptosis / Q000276:immunology*; D002471:Cell Transformation, Neoplastic / Q000276:immunology*; D003110:Colonic Neoplasms / Q000453:epidemiology / Q000517:prevention & control; D015195:Drug Design; D014943:Global Health; D006115:Greece / Q000453:epidemiology; D006801:Humans; D015212:Inflammatory Bowel Diseases / Q000453:epidemiology / Q000276:immunology* / Q000628:therapy; D018664:Interleukin-12 / Q000037:antagonists & inhibitors; D007378:Interleukins / Q000037:antagonists & inhibitors / Q000627:therapeutic use; D007413:Intestinal Mucosa / Q000276:immunology; D009336:Necrosis; D013601:T-Lymphocytes / Q000276:immunology*; D014409:Tumor Necrosis Factor-alpha / Q000037:antagonists & inhibitors; D000093242:Interleukin-6 Inhibitors
D000906:Antibodies; D018664:Interleukin-12; D007378:Interleukins; D014409:Tumor Necrosis Factor-alpha; D000093242:Interleukin-6 Inhibitors