Gp130

Inhibition of gp130

gp130 is an important part of many different types of signaling complexes. Inactivation of gp130 during development is lethal to mice. Homozygous mice who are born show a number of defects including impaired development of the ventricularmyocardium. Haematopoietic effects included reduced numbers of stem cells in the spleen and liver. Loss of gp130 in the adult mouse, either globally or in a tissue-specific manner, is however increasingly linked with beneficial effects in a number of mouse models of disease. Of note, soluble gp130 (sgp130), which was thought a specific inhibitor of IL6 trans signalling, was instead found to inhibit not only IL6 signalling but also multiple other IL6-family cytokines (e.g. OSM, IL11 and CNTF). Thus the widespread benefits of sgp130 in mouse models, and in human trials, may represent the benefits of global (or near global) inhibition of gp130. This suggests gp130 itself as a therapeutic target for human diseases including sepsis, systemic sclerosis, inflammatory bowel disease, among others.