Key result
ENV59-GP3 peptide reduced the disease score in a DSS-induced acute colitis mouse model comparably to the KCa3.1 channel blocker NS6180, and inhibited pro-inflammatory cytokine production.
Why the study?
Peptides derived from human endogenous retrovirus envelope proteins possess immunosuppressive activities, but their effects on immune response in colitis and potassium channel KCa3.1 inhibition required assessment.
Does ENV59-GP3 peptide reduce disease severity and pro-inflammatory cytokine production in a DSS-induced colitis mouse model?
Does ENV59-GP3 peptide reduce disease severity and pro-inflammatory cytokine production in a DSS-induced colitis mouse model?
The retroviral envelope-derived peptide ENV59-GP3 acts as a KCa3.1 channel inhibitor and reduces inflammation in a mouse model of acute colitis, suggesting a novel strategy for treating inflammatory bowel diseases.
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.
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Laska et al. (2022) studied Inflammatory Bowel Diseases / DSS-induced acute colitis. ENV59-GP3 peptide vs. NS6180 was evaluated on Disease score and cytokine production. ENV59-GP3 peptide reduced the disease score in a DSS-induced acute colitis mouse model comparably to the KCa3.1 channel blocker NS6180, and inhibited pro-inflammatory cytokine production.
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