Long Term Delta-9-tetrahydrocannabinol Administration Inhibits Proinflammatory Responses in Minor Salivary Glands of Chronically Simian Immunodeficieny Virus Infected Rhesus Macaques
HIV/SIV-associated oral mucosal disease/dysfunction (HAOMD) (gingivitis/periodontitis/salivary adenitis) represents a major comorbidity affecting HIV patients on anti-retroviral therapy. Using a systems biology approach, we investigated molecular changes (mRNA/microRNA) underlying HAOMD and its modu...
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| Format: | Article |
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MDPI AG
2020-07-01
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| Series: | Viruses |
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| Online Access: | https://www.mdpi.com/1999-4915/12/7/713 |
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| author | Xavier Alvarez Karol Sestak Siddappa N. Byrareddy Mahesh Mohan |
| author_facet | Xavier Alvarez Karol Sestak Siddappa N. Byrareddy Mahesh Mohan |
| author_sort | Xavier Alvarez |
| collection | DOAJ |
| description | HIV/SIV-associated oral mucosal disease/dysfunction (HAOMD) (gingivitis/periodontitis/salivary adenitis) represents a major comorbidity affecting HIV patients on anti-retroviral therapy. Using a systems biology approach, we investigated molecular changes (mRNA/microRNA) underlying HAOMD and its modulation by phytocannabinoids (delta-9-tetrahydrocannabinol (∆<sup>9</sup>-THC)) in uninfected (<i>n</i> = 5) and SIV-infected rhesus macaques untreated (VEH-untreated/SIV; <i>n</i> = 7) or treated with vehicle (VEH/SIV; <i>n</i> = 3) or ∆<sup>9</sup>-THC (THC/SIV; <i>n</i> = 3). Relative to controls, fewer mRNAs were upregulated in THC/SIV compared to VEH-untreated/SIV macaques. Gene enrichment analysis showed differential enrichment of biological functions involved in anti-viral defense, Type-I interferon, Toll-like receptor, RIG-1 and IL1R signaling in VEH-untreated/SIV macaques. We focused on the anti-ER-stress anterior gradient-2 (<i>AGR2</i>), epithelial barrier protecting and anti-dysbiotic WAP Four-Disulfide Core Domain-2 (<i>WFDC2</i>) and glucocorticoid-induced anti-inflammatory <i>TSC22D3</i> (TSC22-domain family member-3) that were significantly downregulated in oropharyngeal mucosa (OPM) of VEH-untreated/SIV macaques. All three proteins localized to minor salivary gland acini and secretory ducts and showed enhanced and reduced expression in OPM of THC/SIV and VEH/SIV macaques, respectively. Additionally, inflammation associated miR-21, miR-142-3p and miR-29b showed significantly higher expression in OPM of VEH-untreated/SIV macaques. <i>TSC22D3</i> was validated as a target of miR-29b. These preliminary translational findings suggest that phytocannabinoids may safely and effectively reduce oral inflammatory responses in HIV/SIV and other (autoimmune) diseases. |
| first_indexed | 2024-03-10T18:45:16Z |
| format | Article |
| id | doaj.art-291e2b38e9794577a42f91873a3489d9 |
| institution | Directory Open Access Journal |
| issn | 1999-4915 |
| language | English |
| last_indexed | 2024-03-10T18:45:16Z |
| publishDate | 2020-07-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Viruses |
| spelling | doaj.art-291e2b38e9794577a42f91873a3489d92023-11-20T05:32:16ZengMDPI AGViruses1999-49152020-07-0112771310.3390/v12070713Long Term Delta-9-tetrahydrocannabinol Administration Inhibits Proinflammatory Responses in Minor Salivary Glands of Chronically Simian Immunodeficieny Virus Infected Rhesus MacaquesXavier Alvarez0Karol Sestak1Siddappa N. Byrareddy2Mahesh Mohan3Southwest National Primate Research Center, Texas Biomedical Research Institute, San Antonio, TX 78227, USAPreCliniTria, LLC., Mandeville, LA 70471, USADepartment of Pharmacology and Experimental Neuroscience, University of Nebraska Medical Center, Omaha, NE 68198, USASouthwest National Primate Research Center, Texas Biomedical Research Institute, San Antonio, TX 78227, USAHIV/SIV-associated oral mucosal disease/dysfunction (HAOMD) (gingivitis/periodontitis/salivary adenitis) represents a major comorbidity affecting HIV patients on anti-retroviral therapy. Using a systems biology approach, we investigated molecular changes (mRNA/microRNA) underlying HAOMD and its modulation by phytocannabinoids (delta-9-tetrahydrocannabinol (∆<sup>9</sup>-THC)) in uninfected (<i>n</i> = 5) and SIV-infected rhesus macaques untreated (VEH-untreated/SIV; <i>n</i> = 7) or treated with vehicle (VEH/SIV; <i>n</i> = 3) or ∆<sup>9</sup>-THC (THC/SIV; <i>n</i> = 3). Relative to controls, fewer mRNAs were upregulated in THC/SIV compared to VEH-untreated/SIV macaques. Gene enrichment analysis showed differential enrichment of biological functions involved in anti-viral defense, Type-I interferon, Toll-like receptor, RIG-1 and IL1R signaling in VEH-untreated/SIV macaques. We focused on the anti-ER-stress anterior gradient-2 (<i>AGR2</i>), epithelial barrier protecting and anti-dysbiotic WAP Four-Disulfide Core Domain-2 (<i>WFDC2</i>) and glucocorticoid-induced anti-inflammatory <i>TSC22D3</i> (TSC22-domain family member-3) that were significantly downregulated in oropharyngeal mucosa (OPM) of VEH-untreated/SIV macaques. All three proteins localized to minor salivary gland acini and secretory ducts and showed enhanced and reduced expression in OPM of THC/SIV and VEH/SIV macaques, respectively. Additionally, inflammation associated miR-21, miR-142-3p and miR-29b showed significantly higher expression in OPM of VEH-untreated/SIV macaques. <i>TSC22D3</i> was validated as a target of miR-29b. These preliminary translational findings suggest that phytocannabinoids may safely and effectively reduce oral inflammatory responses in HIV/SIV and other (autoimmune) diseases.https://www.mdpi.com/1999-4915/12/7/713THCHIV/SIVrhesus macaqueminor salivary gland inflammationmiR-29b |
| spellingShingle | Xavier Alvarez Karol Sestak Siddappa N. Byrareddy Mahesh Mohan Long Term Delta-9-tetrahydrocannabinol Administration Inhibits Proinflammatory Responses in Minor Salivary Glands of Chronically Simian Immunodeficieny Virus Infected Rhesus Macaques Viruses THC HIV/SIV rhesus macaque minor salivary gland inflammation miR-29b |
| title | Long Term Delta-9-tetrahydrocannabinol Administration Inhibits Proinflammatory Responses in Minor Salivary Glands of Chronically Simian Immunodeficieny Virus Infected Rhesus Macaques |
| title_full | Long Term Delta-9-tetrahydrocannabinol Administration Inhibits Proinflammatory Responses in Minor Salivary Glands of Chronically Simian Immunodeficieny Virus Infected Rhesus Macaques |
| title_fullStr | Long Term Delta-9-tetrahydrocannabinol Administration Inhibits Proinflammatory Responses in Minor Salivary Glands of Chronically Simian Immunodeficieny Virus Infected Rhesus Macaques |
| title_full_unstemmed | Long Term Delta-9-tetrahydrocannabinol Administration Inhibits Proinflammatory Responses in Minor Salivary Glands of Chronically Simian Immunodeficieny Virus Infected Rhesus Macaques |
| title_short | Long Term Delta-9-tetrahydrocannabinol Administration Inhibits Proinflammatory Responses in Minor Salivary Glands of Chronically Simian Immunodeficieny Virus Infected Rhesus Macaques |
| title_sort | long term delta 9 tetrahydrocannabinol administration inhibits proinflammatory responses in minor salivary glands of chronically simian immunodeficieny virus infected rhesus macaques |
| topic | THC HIV/SIV rhesus macaque minor salivary gland inflammation miR-29b |
| url | https://www.mdpi.com/1999-4915/12/7/713 |
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