In this section
@article{Widjaja:2024:10.3390/ijms25031363,
author = {Widjaja, AA and Cook, SA},
doi = {10.3390/ijms25031363},
journal = {International Journal of Molecular Sciences},
pages = {1--12},
title = {Nonspecific inhibition of IL6 family cytokine signalling by soluble gp130},
url = {http://dx.doi.org/10.3390/ijms25031363},
volume = {25},
year = {2024}
}
TY - JOUR
AB - IL6 is a proinflammatory cytokine that binds to membrane-bound IL6 receptor (IL6R) or soluble IL6R to signal via gp130 in cis or trans, respectively. We tested the hypothesis that sgp130Fc, which is believed to be a selective IL6 trans-signalling inhibitor, is in fact a non-specific inhibitor of gp130 signalling. In human cancer and primary cells, sgp130Fc inhibited IL6, IL11, OSM and CT1 cis-signalling. The IC50 values of sgp130Fc for IL6 and OSM cis-signalling were markedly (20- to 200-fold) lower than the concentrations of sgp130Fc used in mouse studies and clinical trials. sgp130 inhibited IL6 and OSM signalling in the presence of an ADAM10/17 inhibitor and the absence of soluble IL6R or OSMR, with effects that were indistinguishable from those of a gp130 neutralising antibody. These data show that sgp130Fc does not exclusively block IL6 trans-signalling and reveal instead that broad inhibition of gp130 signalling likely underlies its therapeutic effects. This proposes global or modular inhibition of gp130 as a therapeutic approach for treating human disease.
AU - Widjaja,AA
AU - Cook,SA
DO - 10.3390/ijms25031363
EP - 12
PY - 2024///
SN - 1422-0067
SP - 1
TI - Nonspecific inhibition of IL6 family cytokine signalling by soluble gp130
T2 - International Journal of Molecular Sciences
UR - http://dx.doi.org/10.3390/ijms25031363
UR - https://www.ncbi.nlm.nih.gov/pubmed/38338642
VL - 25
ER -