| Title: |
Nonspecific inhibition of IL6 family cytokine signalling by soluble gp130 |
| Authors: |
Widjaja, AA; Cook, SA |
| Source: |
12 ; 1 |
| Publisher Information: |
MDPI AG |
| Publication Year: |
2024 |
| Collection: |
Imperial College London: Spiral |
| Subject Geographic: |
Switzerland |
| Description: |
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. |
| Document Type: |
article in journal/newspaper |
| Language: |
English |
| Relation: |
International Journal of Molecular Sciences; http://hdl.handle.net/10044/1/109567 |
| DOI: |
10.3390/ijms25031363 |
| Availability: |
http://hdl.handle.net/10044/1/109567; https://doi.org/10.3390/ijms25031363 |
| Rights: |
© 2024 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https:// creativecommons.org/licenses/by/ 4.0/). ; https://creativecommons.org/licenses/by/4.0/ |
| Accession Number: |
edsbas.3505F78F |
| Database: |
BASE |