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Diminazene aceturate (Berenil) downregulates Trypanosoma congolense-induced proinflammatory cytokine production by altering phosphorylation of MAPK and STAT proteins

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Abstract

Diminazene aceturate (Berenil) is the most commonly used trypanolytic agent in livestock. We previously showed that Berenil downregulates Trypanosoma congolense (T. congolense)-induced cytokine production in macrophages both in vitro and in vivo. Here, we investigated the molecular mechanisms through which the drug alters T. congolense-induced cytokine production in macrophages. We show that pretreatment of macrophages with Berenil significantly downregulated T. congolense-induced phosphorylation of mitogen-activated protein kinase (p38), signal transducer and activator of transcription (STAT) proteins including STAT1 and STAT3, and NFκB activity both in vitro and in vivo. Collectively, our results reveal a mechanistic insight through which Berenil downregulates T. congolense-induced cytokine production in macrophages by inhibiting key signaling molecules and pathways associated with proinflammatory cytokine production.

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Authors and Affiliations

  1. Parasite Vaccines Development Laboratory, Department of Immunology, Max Rady College of Medicine, Rady Faculty of Health Sciences, University of Manitoba, 750 McDermot Avenue, Winnipeg, MB, R3E 0T5, Canada

    Shiby M. Kuriakose, Chukwunonso Onyilagha, Rani Singh, Ping Jia & Jude E. Uzonna

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  1. Shiby M. Kuriakose
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  2. Chukwunonso Onyilagha
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  3. Rani Singh
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  4. Ping Jia
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  5. Jude E. Uzonna
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Correspondence to Jude E. Uzonna.

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The University of Manitoba Animal Care Committee approved all studies in accordance with the regulation of the Canadian Council on Animal Care.

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The authors declare that they have no conflict of interest.

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Kuriakose, S.M., Onyilagha, C., Singh, R. et al. Diminazene aceturate (Berenil) downregulates Trypanosoma congolense-induced proinflammatory cytokine production by altering phosphorylation of MAPK and STAT proteins. Immunol Res 67, 84–92 (2019). https://doi.org/10.1007/s12026-018-9040-5

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  • DOI: https://doi.org/10.1007/s12026-018-9040-5

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