Interleukin-6 trans-signaling in inflammatory bowel disease.
The pathogenesis of inflammatory bowel disease (IBD) is complex, involving a wide range of molecules including cytokines. Recent investigations support the important role of an interleukin-6 (IL-6) signaling pathway in the development of IBD. However, the molecular mechanisms of this pathway in the intestine remain incompletely understood. The circulating and intestinal levels of IL-6 as well as soluble IL-6 receptor (sIL-6R) are increased in patients with IBD. It is remarkable that the mucosal T cells of IBD patients are extremely resistant to apoptosis and that a large fraction of these cells express membrane-bound gp130 but not IL-6R. The accumulated evidence strongly supports the hypothesis that the development and perpetuation of IBD relies on the increased formation of IL-6/sIL-6R complexes interacting with membrane-bound gp130 on T cells via trans-signaling. These studies suggest that IL-6 trans-signaling may play a role in the development of IBD; they therefore imply the possibility of a selective therapeutic strategy to target this signaling.
Mitsuyama
Keiichi
K
Division of Gastroenterology, Department of Medicine, Kurume University School of Medicine, Asahi-machi 67, Kurume 830-0011, Japan. ibd@med.kurume-u.ac.jp
Sata
Michio
M
Rose-John
Stefan
S
D000818:Animals; D017209:Apoptosis; D002465:Cell Movement; D015179:Colorectal Neoplasms / Q000209:etiology; D050822:Cytokine Receptor gp130 / Q000494:pharmacology / Q000502:physiology; D006801:Humans; D015212:Inflammatory Bowel Diseases / Q000209:etiology* / Q000503:physiopathology / Q000628:therapy; D015850:Interleukin-6 / Q000502:physiology; D007962:Leukocytes / Q000473:pathology / Q000502:physiology; D051379:Mice; D008954:Models, Biological; D019947:Receptors, Interleukin-6 / Q000502:physiology*; D050796:STAT3 Transcription Factor / Q000502:physiology; D015398:Signal Transduction
C508600:IL6 protein, human; D015850:Interleukin-6; D019947:Receptors, Interleukin-6; D050796:STAT3 Transcription Factor; C494086:STAT3 protein, human; C494087:Stat3 protein, mouse; D050822:Cytokine Receptor gp130