Description
Presentation at the 3rd Workshop of the FET Project PANACHE:The opening of pannexin1 channels is considered as a key event in inflammation. The release of adenosine triphosphate through pannexin1 channels triggers inflammasome signalling and activation of immune cells. By doing so, pannexin1 channels play an important role in several inflammatory diseases. Although pannexin1 channel inhibition could represent a novel clinical strategy for treatment of inflammatory disorders, therapeutic pannexin1 channel targeting is impeded by the lack of specific, potent and/or in vivo-applicable inhibitors.
In this respect, our group identified 3 cross-reactive nanobodies that showed affinity for both murine and human pannexin1 proteins in the nanomolar range. Moreover, the pannexin1-targeting nanobodies were demonstrated to block pannexin1 channel-mediated release of adenosine triphosphate in vitro. Additionally, the pannexin1-targetting nanobodies were found to display anti-inflammatory effects in vitro through reduction of interleukin 1 beta levels. This anti-inflammatory outcome was further confirmed in vivo using a human-relevant mouse model of acute liver disease relying on acetaminophen overdosing. More specifically, the pannexin1-targetting nanobodies reduced serum levels of inflammatory cytokines and attenuated liver damage. These effects were associated with alteration of the expression of several NLRP3 inflammasome components.
In conclusion, this study introduces for the first time specific, potent and in vivo-applicable nanobody-based inhibitors of pannexin1 channels. As demonstrated for the case of liver disease, the pannexin1-targeting nanobodies hold great promise as anti-inflammatory agents, yet this should be further tested for extrahepatic inflammatory disorders.
| Period | 7 Oct 2024 |
|---|---|
| Event title | 3rd online PANACHE workshop |
| Event type | Conference |
| Location | Brussels, BelgiumShow on map |
| Degree of Recognition | International |
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