RNA-seq Analysis of δ9-Tetrahydrocannabinol-treated T Cells Reveals Altered Gene Expression Profiles That Regulate Immune Response and Cell Proliferation.
Marijuana has drawn significant public attention and concern both for its medicinal and recreational use. Δ9-Tetrahydrocannabinol (THC), which is the main bioactive component in marijuana, has also been shown to possess potent anti-inflammatory properties by virtue of its ability to activate cannabinoid receptor-2 (CB-2) expressed on immune cells. In this study, we used RNA-seq to quantify the transcriptomes and transcript variants that are differentially regulated by THC in super antigen-activated lymph node cells and CD4(+) T cells. We found that the expressions of many transcripts were altered by THC in both total lymph node cells and CD4(+) T cells. Furthermore, the abundance of many miRNA precursors and long non-coding RNAs was dramatically altered in THC-treated mice. For example, the expression of miR-17/92 cluster and miR-374b/421 cluster was down-regulated by THC. On the other hand miR-146a, which has been shown to induce apoptosis, was up-regulated by THC. Long non-coding RNAs that are expressed from the opposite strand of CD27 and Appbp2 were induced by THC. In addition, THC treatment also caused alternative promoter usage and splicing. The functions of those altered transcripts were mainly related to immune response and cell proliferation.
From the Department of Pathology, Microbiology and Immunology, School of Medicine, University of South Carolina, Columbia, South Carolina 29209.
Xiaoming
X
Yang
From the Department of Pathology, Microbiology and Immunology, School of Medicine, University of South Carolina, Columbia, South Carolina 29209.
Marpe
M
Bam
From the Department of Pathology, Microbiology and Immunology, School of Medicine, University of South Carolina, Columbia, South Carolina 29209.
Prakash S
PS
Nagarkatti
From the Department of Pathology, Microbiology and Immunology, School of Medicine, University of South Carolina, Columbia, South Carolina 29209 Mitzi.Nagarkatti@uscmed.sc.edu.
Mitzi
M
Nagarkatti
D000818:Animals; D015496:CD4-Positive T-Lymphocytes; D013759:Dronabinol / Q000494:pharmacology*; D005260:Female; D020869:Gene Expression Profiling / Q000379:methods; D005786:Gene Expression Regulation / Q000187:drug effects*; D059014:High-Throughput Nucleotide Sequencing; D051379:Mice; D035683:MicroRNAs / Q000096:biosynthesis* / Q000235:genetics; D005810:Multigene Family; D062085:RNA, Long Noncoding / Q000096:biosynthesis* / Q000235:genetics
D035683:MicroRNAs; D062085:RNA, Long Noncoding; D013759:Dronabinol
T helper cells; cannabinoid; gene expression; immunosuppression; inflammation