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Retroviral Glycoprotein-Mediated Immune Suppression via the potassium Channel KCa3.1- A new strategy for treatment of Inflammatory Bowel Diseases.
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  • Magdalena Laska,
  • Jesper Bonnet Møller,
  • Jonas Heilskov Graversen,
  • Dorte Strøbæk,
  • Linda Blomster,
  • Palle Christophersen,
  • Shervin Bahrami
Magdalena Laska
Aarhus University

Corresponding Author:[email protected]

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Jesper Bonnet Møller
University of Southern Denmark
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Jonas Heilskov Graversen
University of Southern Denmark
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Dorte Strøbæk
Saniona A/S
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Linda Blomster
Saniona A/S
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Palle Christophersen
Saniona A/S
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Shervin Bahrami
Aarhus University
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Abstract

Background and Purpose: Peptides derived from retroviral envelope proteins have been shown to possess a wide range of immunosuppressive and anti-inflammatory activities. We have previously reported identification of such a peptide derived from the envelope protein coded by a human endogenous retrovirus (HERV). In this study we assessed effects of this peptide treatment on inhibition of immune response in the DSS-induced mice model of colitis. Furthermore, we identified that in vitro the peptide inhibits the KCa3.1 potassium channel, a potential target for therapy of immune diseases. Experimental Approach: We characterized an immunosuppressive peptide ENV59, from a specific HERV envelope protein, in vivo effects on inflammation control in acute colitis mice model and in vitro on the production of pro-inflammatory cytokines. Furthermore, we described in vitro ENV59-GP3 effects with respect to potency of inhibition on KCa3.1 channels and calcium influx. Key Results: ENV59-GP3 peptide treatment showed reduction of the disease score in the DSS-induced acute colitis mice model, which was comparable to effects of the KCa3.1 channel blocker NS6180. Analysis of cytokine production from DSS-mice model treated animals revealed equipotent inhibitory effects of the ENV59-GP3 and NS6180 compounds on the production of IL-6, TNF-α, IL-1β. Patch clamp studies show that the peptide ENV59-GP3 is a blocker of the potassium channel KCa3.1. Conclusion and Implications: Env59-GP3 represents KCa3.1 channel inhibitor underlining the implications of using virus derived channel blockers for treatment of autoimmune diseases. There are no drugs with a similar mechanism of action currently on the market.
05 Jan 2022Submitted to British Journal of Pharmacology
07 Jan 2022Submission Checks Completed
07 Jan 2022Assigned to Editor
10 Jan 2022Reviewer(s) Assigned
11 Feb 2022Review(s) Completed, Editorial Evaluation Pending
21 Feb 2022Editorial Decision: Revise Minor