Long Term Delta-9-tetrahydrocannabinol Administration Inhibits Proinflammatory Responses in Minor Salivary Glands of Chronically Simian Immunodeficieny Virus Infected Rhesus Macaques
Abstract
1. Introduction
2. Materials and Methods
2.1. Animal Care, Ethics and Experimental Procedures
2.2. Animal Model and Experimental Design
2.3. Global MicroRNA (miRNA) Profiling
2.4. RNA-Seq Library Construction, Clustering and Sequencing
2.5. Cloning of 3′-UTR of AGR2 and TSC22D3 mRNA and Dual-Glo Luciferase Reporter Gene Assay
2.6. Immunofluorescence for Cellular Localization of AGR2, WFDC2 and TSC22D3 in OPM Tissues
2.7. Quantitative Image Analysis of OPM Sections
2.8. miR-29b Overexpression Studies
2.9. Quantitation of Mucosal Viral Loads
2.10. Data Analysis and Availability
3. Results
3.1. Plasma Viral Loads, CD4+ and CD8+ T Cell Status and Oral Histopathology
3.2. Genes Associated with Anti-Viral Defense, Interferon Signaling and Toll-Like Receptor Signaling Are Markedly Upregulated in OPM of VEH/SIV but not THC/SIV Rhesus Macaques
3.3. Endoplasmic Reticulum Stress (ER) regulator Anterior Gradient 2 (AGR2), Epithelial Barrier Enhancing WAP Four-Disulfide Core Domain Protein 2 (WFDC2) and the Anti-Inflammatory TSC22D3 Are Significantly Downregulated in OPM of VEH-Untreated/SIV Rhesus Macaques
3.4. Chronic THC Administration Preserved AGR2, WFDC2 and TSC22D3 Protein Expression in Minor Salivary Glands (MiSGs) of Chronic SIV-Infected Rhesus Macaques
3.5. TSC22D3 Is Post-Transcriptionally Regulated by miR-29b
4. Discussion
Supplementary Materials
Author Contributions
Funding
Acknowledgments
Conflicts of Interest
References
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Animal ID | SIV Inoculum | Duration of Infection | Plasma Viral Loads 106/mL | OPM Viral Loads 106/mg RNA | Opportunistic Infections |
---|---|---|---|---|---|
Chronic SIV-Infected and Vehicle Untreated (Group 1) for microRNA and gene expression studies | |||||
P763 # | SIVmac251 | 145 | NA | 3 | ND |
JJ71 # * | SIVmac239 | 148 | NA | 0.3 | ND |
JR60 # * | SIVmac251 | 180 | NA | 10 | ND |
JR15 # * | SIVmac251 | 180 | NA | 0.3 | ND |
KA05 # * | SIVmac251 | 90 | NA | 0.7 | ND |
JP38 # * | SIVmac251 | 180 | NA | 0.1 | ND |
JD59 # * | SIVmac251 | 150 | NA | 300 | ND |
IJ60 * | SIVmac251 | 180 | NA | NA | ND |
Chronic SIV-Infected and Vehicle treated (Group 2) for Immunofluorescence studies | |||||
JH47 % | SIVmac251 | 180 | 2 | NA | ND |
JR36 % | SIVmac251 | 180 | 0.5 | 0.02 | ND |
JD66 % | SIVmac251 | 180 | 0.04 | 0.5 | ND |
Chronic SIV-Infected and ∆9-THC treated (Group 3) for Immunofluorescence studies | |||||
JI45 # % * | SIVmac251 | 180 | 3 | 0.02 | ND |
JT80 # % * | SIVmac251 | 180 | 1 | 9 | ND |
IV90 # % * | SIVmac251 | 180 | 0.02 | 0.3 | ND |
Uninfected Controls (Group 4) for microRNA and gene expression studies | |||||
JC65 # * | NA | NA | NA | NA | NA |
GJ01 # * | NA | NA | NA | NA | NA |
GK11 # * | NA | NA | NA | NA | NA |
GK22 # * | NA | NA | NA | NA | NA |
JD95 # * | NA | NA | NA | NA | NA |
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Alvarez, X.; Sestak, K.; Byrareddy, S.N.; Mohan, M. Long Term Delta-9-tetrahydrocannabinol Administration Inhibits Proinflammatory Responses in Minor Salivary Glands of Chronically Simian Immunodeficieny Virus Infected Rhesus Macaques. Viruses 2020, 12, 713. https://doi.org/10.3390/v12070713
Alvarez X, Sestak K, Byrareddy SN, Mohan M. Long Term Delta-9-tetrahydrocannabinol Administration Inhibits Proinflammatory Responses in Minor Salivary Glands of Chronically Simian Immunodeficieny Virus Infected Rhesus Macaques. Viruses. 2020; 12(7):713. https://doi.org/10.3390/v12070713
Chicago/Turabian StyleAlvarez, Xavier, Karol Sestak, Siddappa N. Byrareddy, and Mahesh Mohan. 2020. "Long Term Delta-9-tetrahydrocannabinol Administration Inhibits Proinflammatory Responses in Minor Salivary Glands of Chronically Simian Immunodeficieny Virus Infected Rhesus Macaques" Viruses 12, no. 7: 713. https://doi.org/10.3390/v12070713
APA StyleAlvarez, X., Sestak, K., Byrareddy, S. N., & Mohan, M. (2020). Long Term Delta-9-tetrahydrocannabinol Administration Inhibits Proinflammatory Responses in Minor Salivary Glands of Chronically Simian Immunodeficieny Virus Infected Rhesus Macaques. Viruses, 12(7), 713. https://doi.org/10.3390/v12070713