Therapeutic strategies for targeting the IL-6/STAT3 cytokine signaling pathway in inflammatory bowel disease.
Interleukin-6 (IL-6) is a pleiotropic cytokine with central roles in immune and inflammatory reactions. IL-6 first binds to the IL-6 receptor (IL-6R), this complex then associates with gp130, inducing dimerization and the initiation of signaling through signal transducer and activator of transcription-3 (STAT3). Notably, the combination of soluble IL-6 receptor (sIL-6R) and IL-6 stimulates cells that only express gp130 and not IL-6R, a process known as trans-signaling. In contrast, soluble gpl30 (sgp130) serves as a natural inhibitor of trans-signaling. Accumulated evidence strongly supports the hypothesis that the development and perpetuation of inflammatory bowel disease (IBD) relies on IL-6-mediated STAT3 activation on mucosal T-cells. This review looks at therapeutic strategies targeting the IL-6/STAT3 pathway in patients with IBD, including strategies involving the anti-IL-6 receptor antibody and soluble gp130Fc.
Mitsuyama
Keiichi
K
Division of Gastroenterology, Department of Medicine, Kurume University School of Medicine, Asahi-machi 67, Kurume, Japan. ibd@med.kurume-u.ac.jp
Matsumoto
Satoshi
S
Masuda
Junya
J
Yamasakii
Hiroshi
H
Kuwaki
Kotaro
K
Takedatsu
Hidetoshi
H
Sata
Michio
M
D050822:Cytokine Receptor gp130 / Q000378:metabolism; D016503:Drug Delivery Systems; D006801:Humans; D015212:Inflammatory Bowel Diseases / Q000188:drug therapy / Q000378:metabolism*; D015850:Interleukin-6 / Q000378:metabolism*; D008954:Models, Biological; D050796:STAT3 Transcription Factor / Q000037:antagonists & inhibitors / Q000378:metabolism*; D015398:Signal Transduction; D000093242:Interleukin-6 Inhibitors
D050822:Cytokine Receptor gp130; D015850:Interleukin-6; D050796:STAT3 Transcription Factor; D000093242:Interleukin-6 Inhibitors; C494086:STAT3 protein, human