| Autor: |
Kumar, Vinay, Torben, Workineh, Mansfield, Joshua, Alvarez, Xavier, Vande Stouwe, Curtis, Li, Jian, Byrareddy, Siddappa N., Didier, Peter J., Pahar, Bapi, Molina, Patricia E., Mohan, Mahesh |
| Předmět: |
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| Zdroj: |
Frontiers in Immunology; 4/30/2019, pN.PAG-N.PAG, 23p |
| Abstrakt: |
Cannabis use is frequent in HIV-infected individuals for its appetite stimulation and anti-inflammatory effects. To identify the underlying molecular mechanisms associated with these effects, we simultaneously profiled micro-RNA (miRNA) and mRNA expression in the colon of chronically simian immunodeficiency virus (SIV)-infected rhesus macaques administered either vehicle (VEH/SIV; n = 9) or Δ9-tetrahydrocannabinol (Δ9-THC; THC/SIV; n = 8). Pro-inflammatory miR-130a, miR-222, and miR-29b, lipopolysaccharide-responsive miR-146b-5p and SIV-induced miR-190b were significantly upregulated in VEH/SIV rhesus macaques. Compared to VEH/SIV rhesus macaques, 10 miRNAs were significantly upregulated in THC/SIV rhesus macaques, among which miR-204 was confirmed to directly target MMP8, an extracellular matrix-degrading collagenase that was significantly downregulated in THC/SIV rhesus macaques. Moreover, THC/SIV rhesus macaques failed to upregulate pro-inflammatory miR-21, miR-141 and miR-222, and alpha/beta-defensins, suggesting attenuated intestinal inflammation. Further, THC/SIV rhesus macaques showed higher expression of tight junction proteins (occludin, claudin-3), anti-inflammatory MUC13 , keratin-8 (stress protection), PROM1 (epithelial proliferation), and anti-HIV CCL5. Gomori one-step trichrome staining detected significant collagen deposition (fibrosis) in the paracortex and B cell follicular zones of axillary lymph nodes from all VEH/SIV but not in THC/SIV rhesus macaques, thus demonstrating the ability of Δ9-THC to prevent lymph node fibrosis, a serious irreversible consequence of HIV induced chronic inflammation. Furthermore, using flow cytometry, we showed that Δ9-THC suppressed intestinal T cell proliferation/activation (Ki67/HLA-DR) and PD-1 expression and increased the percentages of anti-inflammatory CD163+ macrophages. Finally, while Δ9-THC did not affect the levels of CD4+ T cells, it significantly reduced absolute CD8+ T cell numbers in peripheral blood at 14 and 150 days post-SIV infection. These translational findings strongly support a role for differential miRNA/gene induction and T cell activation in Δ9-THC-mediated suppression of intestinal inflammation in HIV/SIV and potentially other chronic inflammatory diseases of the intestine. [ABSTRACT FROM AUTHOR] |
| Databáze: |
Complementary Index |
| Externí odkaz: |
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