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Define the effects and mechanism of THC and CBD on IFN-I mediated inflammation and immune dysfunction during HIV infection

明确THC和CBD对HIV感染期间IFN-I介导的炎症和免疫功能障碍的影响和机制

基本信息

批准号：
10267753
负责人：
SCOTT G KITCHEN
金额：
$ 37.05万
依托单位：
UNIVERSITY OF CALIFORNIA LOS ANGELES
依托单位国家：
美国
项目类别：
财政年份：
2020
资助国家：
美国
起止时间：
2020-09-30 至 2025-07-31
项目状态：
未结题

来源：
https://reporter.nih.gov/project-details/10267753
关键词：
Affect Agonist Analgesics Animals Anti-Inflammatory Agents Antigen-Presenting Cells Antiinflammatory Effect Antiviral Agents Antiviral Response Automobile Driving Binding Biological CNR1 gene CNR2 gene Cannabidiol Cannabinoids Cannabis Cannabis sativa plant Cardiovascular Diseases Cells Chronic Clinical Management Clinical Trials Clustered Regularly Interspaced Short Palindromic Repeats Complex Conflict (Psychology)Dendritic Cells Disease Disease Progression Drug usage Frequencies Functional disorder Gene Expression Genes HIV HIV Infections HIV-1 HIV-associated neurocognitive disorder Human Immune Immune System Diseases Immune system Immunocompetence In Vitro Individual Infection Inflammation Inflammatory Interferon Type I Interferon-alpha Interferons Knock-out Macaca mulatta Malignant Neoplasms Mediating Microglia Neuraxis Neurodegenerative Disorders Pathogenesis Patients Plasma Play Predisposition Property Reporting Role SIV Signal Pathway Signal Transduction Specimen T cell response T-Lymphocyte Tetrahydrocannabinol United States Viral Viral Load result Virus Replication antiretroviral therapy cannabinoid receptor cell type chronic inflammatory disease comorbidity cytokine dosage endogenous cannabinoid system exhaustion high dimensionality humanized mouse immune activation immune function immunoregulation improved in vivo knock-down latent HIV reservoir macrophage marijuana use monocyte mouse model prevent receptor response small hairpin RNA

项目摘要

Project Summary One of the hallmarks of HIV infection is chronic immune activation/inflammation, which is strongly associated with and predictive of HIV disease progression, even in patients that were successfully treated with anti-retroviral therapy (ART). We and other have shown that chronic elevation of type I IFN signaling in HIV+ individuals is a major driver in immune activation. Alleviating chronic activation may reduce disease progression and prevent or slow down progression of HIV-associated diseases, including HIV-associated neurocognitive disorders (HAND), which is fueled by inflammation in the central nervous system (CNS). In recent years, studies have suggested that major components of cannabis, namely THC and CBD, may have anti-inflammatory properties. However, the individual and combined effects and mechanisms of THC and CBD on immune activation during HIV infection remain elusive. In this project, we aim to study the individual and combined effects of THC and CBD on immune cell activation and CNS inflammation during HIV infection. We hypothesize that THC and CBD regulate IFN-I mediated inflammation differently by binding to and signaling through diverse cannabinoid receptors. We will carefully evaluate if treatment of THC and CBD have the potential to reduce chronic inflammation and improve immune function against HIV infection.

项目总结