miR-199a-3p and miR-100-5p regulate mTOR pathway and inhibit Concanavalin-induced autoimmune hepatitis in mice treated with Δ⁸-THC

---

Presentation Time: 11:30 AM - 12:45 PM
Poster Board Number: B873
Abstract ID: 6081

Presenting Author:
Hamida Hamida , Student at Univ. of South Carolina Sch. of Med., Columbia

Abstract:

MicroRNAs (miRNAs), small endogenous noncoding RNAs, have been shown to have important roles in regulating immune response in autoimmune diseases including autoimmune hepatitis (AIH). In the current study, we investigated if Δ⁸-THC treatment, an ingredient in marijuana, prevents AIH in murine model by altering the epigenetic modulators, miRNAs. Towards this, C57BL/6 mice were i.v. administered Concanavalin A (ConA;12.5mg/Kg) to induce AIH. Mice were then i.p. treated with Δ⁸-THC (20mg/Kg) or vehicle. We found elevated ALT, AST, IL-6, IFNγ and TNFα in AIH mice which was reversed following Δ⁸-THC treatment. miRNA sequencing revealed miR-199a-3p and miR-100-5, two of the most highly expressed miRNAs in normal liver, were downregulated in ConA-exposed mice, and their decrease correlated with proinflammatory immune response whereas administration of Δ8-THC in AIH mice restored these miRNAs. Ingenuity Pathway Analysis revealed mTOR, a master regulator of inflammatory response, as a target of these miRNAs. We corroborated the increased expression of miR-199a-3p and miR-100-5 and decreased expression of mTOR in AIH mice treated with Δ⁸-THC using qRT-PCR. Transfection of cells with miR-199a-3p and miR-100-5 mimics and inhibitors validated their biological consequences on the repression/expression of mTOR as their potential target. These data suggest the therapeutic role of miR-199a-3p and miR-100-5 by targeting mTOR pathway following treatment with Δ8-THC in experimental AIH.