Micrornas Expression Induces Apoptosis Of Macrophages In Response To Leishmania Major (Mrho/Ir/75/Er): An In-Vitro And In-Vivo Study

IRANIAN JOURNAL OF PARASITOLOGY(2020)

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摘要
Background: We aimed to investigate the effect of miR-15a mimic and inhibitor of miR-155 expression on apoptosis induction in macrophages infected with Iranian strain of Leishmania major in-vitro and in-vivo.Methods: RAW 264.7 cells were infected with L. major promastigotes (MRHO/IR/75/ER), and then were treated with miRNAs. For in-vivo experiment, BALB/c mice were inoculated with L. major promastigotes, and then they were treated with miRNAs. For evaluation of miRNA therapeutic effect, in-vitro and in-vivo studies were performed using quantitative Real-time PCR, How cytometry, lesion size measurement, and Limiting Dilution Assay (LDA). This study was performed in Shahid Beheshti University of Medical Sciences in 2019.Results: In-vitro results of flow cytometry showed that using miR-15a mimic, miR-155 inhibitor In vivo or both of them increased apoptosis of macrophages. In in-vivo, size of lesion increased during experiment in control groups (P<0.05) while application of both miR-155 inhibitor and miR-15a mimic inhibited the increase in the size of lesions within 6 wk of experiment (P=0.85). LDA results showed that microRNA therapy could significantly decrease parasite load in mimic or inhibitor receiving groups compared to the control group (P<0.05).Conclusion: miR-155 inhibitor and miR-15a mimic in L major infected macrophages can induce apoptosis and reduce parasite burden. Therefore, miRNA-based therapy can be proposed as new treatment for cutaneous leishmaniasis.
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关键词
Leishmania major, Apoptosis, microRNAs, In vitro, In vivo
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