Projects per year
Abstract
Background and aims: Pannexins constitute a relative new family of transmembrane proteins that form channels linking the cytoplasmic compartment with the extracellular environ- ment. Recent research showed that pannexin1 channel inhibi- tion alleviates acetaminophen-induced hepatotoxicity in mice. However, the mechanisms underlying this observation are not entirely clear. On the other hand, monocyte migration has been reported to be mediated in part by pannexin1-depentent ade- nosine triphosphate release in vitro and fine-tuned chemotactic responses of neutrophils seem to require pannexin1 signaling. To check if this also holds true in vivo, in casu in a model of acetaminophen-induced hepatotoxicity, leukocyte recruitment was monitored following inhibition of pannexin1 channel opening. Methods: C57BL/6J mice were overdosed with acet- aminophen followed by treatment with the pannexin1 channel inhibitor 10Panx1 after 1.5 hours. Sampling was performed 6 and 24 hours after acetaminophen administration. In addition to the evaluation of clinically relevant read-outs, such as serum aminotransaminase and cytokine levels, hepatic quantities of inflammatory monocytes (CD45+CD11bhiLy6ChiF4/80lo cells), neutrophils (CD45+CD11bhiLy6G+ cells) and Kupffer cells (CD45+Ly6G-F4/80hiCD11bint cells) were measured using flow cytometric analysis. Tumor necrosis factor α content of these particular cell populations was assessed in parallel. Results: Compared to untreated animals, acetaminophen-overdosed mice showed less Kupffer cells, but increased numbers of liver neutrophils and monocytes. Upon blockage of pannexin1 channels, a significantly reduced amount of neutrophils were recruited to the liver, while no differences were observed in the number of monocytes and Kupffer cells. Concomitantly, diminished tumor necrosis factor α production by monocytes was measured following pannexin1 channel inhibition. Conclusion: These results suggest the involvement of pannexin1 channels in neutrophil recruitment and tumor necrosis factor α production by monocytes during acetaminophen-induced hepatotoxicity in mice.
Original language | English |
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Article number | 697 |
Number of pages | 1 |
Journal | Hepatology |
Volume | 64 |
Issue number | s1 |
Publication status | Published - 1 Nov 2016 |
Event | The Liver Meeting 2016 of the American Association for the Study on Liver Diseases - John B. Hynes Veterans Memorial Convention Center, Boston, United States Duration: 11 Nov 2016 → 15 Nov 2016 http://www.aasld.org/events-professional-development/liver-meeting |
Keywords
- hepatology
- liver
- acetaminophen
- pannexin
- neutrophils
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OZR2651: International Joint Research Group - Liver Connexin and Pannexin Research Group (LCPR)
Vinken, M., Rogiers, V., Cogliati, B. & Dagli, M. L.
1/08/14 → 1/07/26
Project: Fundamental
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OZR2813: Bilaterale samenwerking ikv gemeenschappelijke doctoraatsproject: Bench Fee voor Joint PhD VUB-Universidade de Sao Paulo, Michael Maes
10/06/15 → 31/07/17
Project: Fundamental
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EU457: CONNECT: Connexin and pannexin channels as drug targets and biomarkers in acute and chronic liver disease
1/03/14 → 28/02/19
Project: Fundamental
Research output
- 2 Article
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Pannexin1 as mediator of inflammation and cell death
Crespo Yanguas, S., Willebrords, J., Johnstone, S. R., Maes, M., Decrock, E., De Bock, M., Leybaert, L., Cogliati, B. & Vinken, M., 2017, In: Biochemica et Biophysica Acta - Molecular Cell Research. 1864, 1, p. 51-61 11 p.Research output: Contribution to journal › Article › peer-review
Open Access85 Citations (Scopus) -
Connexin and pannexin signaling in gastrointestinal and liver disease
Maes, M., Crespo Yanguas, S., Willebrords, J., Cogliati, B. & Vinken, M., 1 Oct 2015, In: Translational Research. 166, 4, p. 332-343Research output: Contribution to journal › Article › peer-review
41 Citations (Scopus)