Cannabinoid attenuation of intestinal inflammation in chronic simian immunodeficiency virus (SIV)-infected rhesus macaques involves differential modulation of pro-inflammatory microRNA/gene expression and T-cell activation

We profiled and characterized mRNA expression in colon of 12 chronically SIV-infected rhesus macaques (RMs) receiving vehicle (n=7) or delta-9-tetrahydrocannabinol (THC) and 4 uninfected control macaques. Further analysis identified significant downregulation of genes associated with ion transport, epithelial barrier integrity/function, protection against oxidative injury, double stranded DNA damage repair and autophagy. Similarly, mRNA expression of genes associated with interferon response, anti-microbial defense, apoptosis, oxidative DNA damage, endoplasmic reticulum stress and inflammasome signaling were markedly upregulated. Colon tissue was harvested from 12 chronically SIV-infected (7 VEH-SIV and 5 THC-SIV) and 4 control Indian rhesus macaques. Intact colon tissue was lysed in Qiazol solution (Qiagen Inc) for total RNA extraction. Comparisons in gene expression were made between VEH-SIV and controls, THC-SIV and controls and VEH-SIV relative to THC-SIV macaques.