Alcohol and Cannabinoids Differentially Affect HIV Infection and Function of Human Monocyte-Derived Dendritic Cells (MDDC)

Agudelo, Marisela; Figueroa, Gloria; Yndart, Adriana; Casteleiro, Gianna; Muñoz, Karla; Samikkannu, Thangavel; Atluri, Venkata Subba Rao; Nair, Madhavan

doi:10.3389/fmicb.2015.01452

Cited by 15 publications

(15 citation statements)

References 56 publications

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“…Ethanol (20 mM) treatment alone showed a 20.6% increase in HIV replication compared to control (t(6) = 5.9, p = 0.001, student t test, Fig. 4), which is in line with the previous studies (21,22). Cells that were exposed to DRV alone or along with RTV exhibited approximately a 60% decrease in HIV replication ( p = 0.05 compared to control).…”

Section: Resultssupporting

confidence: 90%

Influence of Ethanol on Darunavir Hepatic Clearance and Intracellular PK/PD in HIV-Infected Monocytes, and CYP3A4-Darunavir Interactions Using Inhibition and in Silico Binding Studies

et al. 2017

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Purpose Although the prevalence of alcohol consumption is higher in HIV+ people than general public, limited information is available on how alcohol affects the metabolism and bioavailability of darunavir (DRV). Methods DRV was quantified by using LC-MS/MS method. All in vitro experiments were performed using human liver microsomes and HIV-infected monocytic cells. CYP3A4 and DRV/ Ritonavir (RTV) docking was performed using GOLD suite 5.8. Results Ethanol (20 mM) significantly decreased apparent half-life and increased degradation rate constant of RTV-boosted DRV but not for DRV alone. Similarly, ethanol exposure increased hepatic intrinsic clearance for RTV-boosted DRV with no significant influence on DRV alone. Ethanol showed a limited influence on intracellular total DRV exposure in the presence of RTV without altering maximum concentration (Cmax) values in HIV-infected monocytic cells. Ethanol alone elevated HIV replication but this effect was nullified with the addition of DRV or DRV + RTV. Additionally, inhibitory potency of DRV was significantly reduced in the presence of ethanol. Our docking results projected that ethanol increases the average distance between DRV and CYP3A4 heme, and alter the orientation of DRV-CYP3A4 binding. Conclusions Collectively these findings suggest that DRV metabolism is primarily influenced by ethanol in the liver, but has minor effect in HIV-residing monocytes.

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Section: Resultssupporting

confidence: 90%

Influence of Ethanol on Darunavir Hepatic Clearance and Intracellular PK/PD in HIV-Infected Monocytes, and CYP3A4-Darunavir Interactions Using Inhibition and in Silico Binding Studies

et al. 2017

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“…Other reports suggest CB 2 agonists suppress HIV replication in macrophages without altering surface receptor expression, primarily by suppressing HIV pol expression [ 135 , 140 ]. HIV infection in monocyte-derived dendritic cells is also attenuated by cannabinoids [ 145 ]. Thus, cannabinoid disruption of HIV replication in monocyte-derived cells mirrors that in T lymphocytes with distinct observation of surface receptor and transcription-based inhibition.…”

Section: Cannabinoids × Hiv: Receptor- and Cell-specific Mechanisms In Preclinical Modelsmentioning

confidence: 99%

Confound, Cause, or Cure: The Effect of Cannabinoids on HIV-Associated Neurological Sequelae

Starr

Jordan‐Sciutto

Mironets

2021

Viruses

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The persistence of human immunodeficiency virus-1 (HIV)-associated neurocognitive disorders (HAND) in the era of effective antiretroviral therapy suggests that modern HIV neuropathogenesis is driven, at least in part, by mechanisms distinct from the viral life cycle. Identifying more subtle mechanisms is complicated by frequent comorbidities in HIV+ populations. One of the common confounds is substance abuse, with cannabis being the most frequently used psychoactive substance among people living with HIV. The psychoactive effects of cannabis use can themselves mimic, and perhaps magnify, the cognitive deficits observed in HAND; however, the neuromodulatory and anti-inflammatory properties of cannabinoids may counter HIV-induced excitotoxicity and neuroinflammation. Here, we review our understanding of the cross talk between HIV and cannabinoids in the central nervous system by exploring both clinical observations and evidence from preclinical in vivo and in vitro models. Additionally, we comment on recent advances in human, multi-cell in vitro systems that allow for more translatable, mechanistic studies of the relationship between cannabinoid pharmacology and this uniquely human virus.

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“…Second, due to the aforementioned “transgenerational” effects ( 168 – 171 ), in an “ideal” clinical study, inclusion/exclusion criteria should also consider “family history” of marijuana consumption. Third, purity/quality of the self-administered marijuana, as well as exposure to other illicit drugs, to alcohol ( 184 ), or to drugs belonging to the “gray zone,” e.g., novel psychoactive substances [NPS, a.k.a. “designer drugs”; synthetic, psychoactive substances that are generally not (yet) under international regulatory control, and among which several synthetic cannabinoids are now present at the black market ( 185 )] should also be explored, since these all can deeply influence immunological effects of acutely applied pCBs, thereby falsifying the results [e.g., acute application of pCBs was found to significantly inhibit both the basal and C-C motif chemokine ligand 2 (CCL2)-stimulated migration of monocytes, but only in individuals non-naive to Cannabis ( 186 )].…”

Section: Open Questions Future Challenges and Perspectivesmentioning

confidence: 99%

Targeting Cannabinoid Signaling in the Immune System: “High”-ly Exciting Questions, Possibilities, and Challenges

2017

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It is well known that certain active ingredients of the plants of Cannabis genus, i.e., the “phytocannabinoids” [pCBs; e.g., (−)-trans-Δ9-tetrahydrocannabinol (THC), (−)-cannabidiol, etc.] can influence a wide array of biological processes, and the human body is able to produce endogenous analogs of these substances [“endocannabinoids” (eCB), e.g., arachidonoylethanolamine (anandamide, AEA), 2-arachidonoylglycerol (2-AG), etc.]. These ligands, together with multiple receptors (e.g., CB1 and CB2 cannabinoid receptors, etc.), and a complex enzyme and transporter apparatus involved in the synthesis and degradation of the ligands constitute the endocannabinoid system (ECS), a recently emerging regulator of several physiological processes. The ECS is widely expressed in the human body, including several members of the innate and adaptive immune system, where eCBs, as well as several pCBs were shown to deeply influence immune functions thereby regulating inflammation, autoimmunity, antitumor, as well as antipathogen immune responses, etc. Based on this knowledge, many in vitro and in vivo studies aimed at exploiting the putative therapeutic potential of cannabinoid signaling in inflammation-accompanied diseases (e.g., multiple sclerosis) or in organ transplantation, and to dissect the complex immunological effects of medical and “recreational” marijuana consumption. Thus, the objective of the current article is (i) to summarize the most recent findings of the field; (ii) to highlight the putative therapeutic potential of targeting cannabinoid signaling; (iii) to identify open questions and key challenges; and (iv) to suggest promising future directions for cannabinoid-based drug development.

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Alcohol and Cannabinoids Differentially Affect HIV Infection and Function of Human Monocyte-Derived Dendritic Cells (MDDC)

Cited by 15 publications

References 56 publications

Influence of Ethanol on Darunavir Hepatic Clearance and Intracellular PK/PD in HIV-Infected Monocytes, and CYP3A4-Darunavir Interactions Using Inhibition and in Silico Binding Studies

Influence of Ethanol on Darunavir Hepatic Clearance and Intracellular PK/PD in HIV-Infected Monocytes, and CYP3A4-Darunavir Interactions Using Inhibition and in Silico Binding Studies

Confound, Cause, or Cure: The Effect of Cannabinoids on HIV-Associated Neurological Sequelae

Targeting Cannabinoid Signaling in the Immune System: “High”-ly Exciting Questions, Possibilities, and Challenges

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