Marisela Agudelo - Academia.edu (original) (raw)

Papers by Marisela Agudelo

Alcoholism: Clinical and Experimental Research, 2014

This commentary is to highlight the relevance and public interest of the review published by Silv... more This commentary is to highlight the relevance and public interest of the review published by Silverstein and Kumar, which focuses on the mechanisms by which alcohol and HIV-1 infection cause increased in central nervous system (CNS) damage. The overall review is based on previous literature with cell culture systems and animal models that have demonstrated that exposure to alcohol and HIV infection or HIV viral proteins result in synergistic up-regulation of pro-inflammatory cytokines and oxidative stress. The authors discuss the effects of alcohol on cells in the CNS, followed by a brief discussion on the impact of HIV-1 and HIV proteins on the CNS, and the final section focuses on the combined effects of HIV and alcohol on the CNS as determined by in vitro, in vivo, and clinical studies.

PloS one, 2016

Epigenetic mechanisms have been shown to play a role in alcohol use disorders (AUDs) and may prov... more Epigenetic mechanisms have been shown to play a role in alcohol use disorders (AUDs) and may prove to be valuable therapeutic targets. However, the involvement of histone deacetylases (HDACs) on alcohol-induced oxidative stress of human primary monocyte-derived dendritic cells (MDDCs) has not been elucidated. In the current study, we took a novel approach combining ex vivo, in vitro and in silico analyses to elucidate the mechanisms of alcohol-induced oxidative stress and role of HDACs in the periphery. ex vivo and in vitro analyses of alcohol-modulation of class I HDACs and activity by MDDCs from self-reported alcohol users and non-alcohol users was performed. Additionally, MDDCs treated with alcohol were assessed using qRT-PCR, western blot, and fluorometric assay. The functional effects of alcohol-induce oxidative stress were measured in vitro using PCR array and in silico using gene expression network analysis. Our findings show, for the first time, that MDDCs from self-reported...

Frontiers in microbiology, 2015

During human immunodeficiency virus (HIV) infection, alcohol has been known to induce inflammatio... more During human immunodeficiency virus (HIV) infection, alcohol has been known to induce inflammation while cannabinoids have been shown to have an anti-inflammatory role. For instance cannabinoids have been shown to reduce susceptibility to HIV-1 infection and attenuate HIV replication in macrophages. Recently, we demonstrated that alcohol induces cannabinoid receptors and regulates cytokine production by monocyte-derived dendritic cells (MDDC). However, the ability of alcohol and cannabinoids to alter MDDC function during HIV infection has not been clearly elucidated yet. In order to study the potential impact of alcohol and cannabinoids on differentiated MDDC infected with HIV, monocytes were cultured for 7 days with GM-CSF and IL-4, differentiated MDDC were infected with HIV-1Ba-L and treated with EtOH (0.1 and 0.2%), THC (5 and 10 μM), or JWH-015 (5 and 10 μM) for 4-7 days. HIV infection of MDDC was confirmed by p24 and Long Terminal Repeats (LTR) estimation. MDDC endocytosis assa...

Journal of alcoholism and drug dependence, 2015

The role of platelets in the neurological diseases that underlie cognitive impairment has attract... more The role of platelets in the neurological diseases that underlie cognitive impairment has attracted increasing attention in recent years. Multiple pathways in platelets contribute to host defenses, as well as to CNS function. In the current study, we hypothesize that the Blood Brain Barrier (BBB) is disrupted when exposed to platelets from patients with triple Co-morbidity (hazardous alcohol users+ HIV+ thrombocytopenia), compared to those with dual, single or no morbidity (HIV only, alcohol only or healthy controls).

International Journal of Nanomedicine, 2015

In the late nineteenth century, Paul Langerhans discovered Langerhans cells, a form of dendritic ... more In the late nineteenth century, Paul Langerhans discovered Langerhans cells, a form of dendritic cell (DC) found on the skin. However, the term DC was first described in 1973 by Ralph M. Steinman after identifying a population of dendritic-shaped cells in the spleen of mice. Increased research on DC lead to the recognition of DCs as professional antigen presenting cells (APCs). DCs can be classified into different subsets based on their location, marker expression, immune function, and cytokine secretion. To date, four major DC subtypes have been identified: myeloid (mDCs) and plasmacytoid (pDCs) in the blood, follicular dendritic cells (FDCs) in lymph follicles, and Langerhans cells in tissues such as the skin and mucosal epithelial. DCs comprise ≤2% of total peripheral-blood mononuclear cells (PBMCs). However, due to their role in the regulation of the adaptive immune response and their localization, DCs have been recognized as the first line of defense against any pathogen includ...

Journal of Alcoholism & Drug Dependence, 2015

Due to the legalization of marijuana and the increased demand for cannabis and alcohol consumptio... more Due to the legalization of marijuana and the increased demand for cannabis and alcohol consumption, research efforts highlighting the biomedical consequences of the use of alcohol and cannabinoids are not only relevant to the substance abuse scientific field, but are also of public health interest. Moreover, an overview of the recent literature about alcohol and cannabinoids neuro-immunomodulatory effects highlighting their future therapeutic potentials will provide a significant contribution to science and medicine. Therefore, in the current review, we will first discuss briefly the prevalence of alcohol and marijuana abuse, followed by a discussion on the individual effects of alcohol and cannabinoids on the immune system; then, we will focus on the role of endocannabinoids on the alcohol-induced inflammatory effects. In addition, the review also incorporates cytokine array data obtained from human monocyte-derived dendritic cells, providing a different perspective on the alcohol and cannabinoid abuse divergent effects on cytokine production. The final section will highlight the therapeutic potential of cannabinoid receptors and the novel strategies to treat alcohol dependence as determined by in vitro, in vivo and clinical studies.

Frontiers in Microbiology, 2015

ACS chemical neuroscience, Jan 25, 2015

In present research work, for the first time we demonstrated that neuropathogenesis in HIV-1 clad... more In present research work, for the first time we demonstrated that neuropathogenesis in HIV-1 clade B & C infection is associated with IL-33 and ST2 dysregulation i.e., implication towards neuropathogenesis. It is known that neuropathogenesis of HIV infected individuals is clade dependent. Pro-inflammatory cytokines and related receptors played a significant role in the complex regulatory mechanisms of neuropathogenesis in HIV-1 infection. Among them, IL-33 is an inflammatory cytokine expressed in the central nervous system (CNS) activates microglia cells and may affect neuroimmune inflammatory processes involved in HIV neuropathogenesis. Beside this, IL-33 receptor (ST2) plays a role in neuroinflammatory processes through the modulation of the biological action of IL-33. qRT-PCR, ELISA, western blot (WB) and flow cytometry experiments were performed to elucidate the role of IL-33/ST2 in HIV neuropathogenesis in CNS cell. Apoptosis and mechanisms of IL-33 in neuronal cells were studi...

Scientific Reports, 2015

HIV subtypes or clades differentially induce HIV-associated neurocognitive disorders (HAND) and s... more HIV subtypes or clades differentially induce HIV-associated neurocognitive disorders (HAND) and substance abuse is known to accelerate HIV disease progression. The HIV-1 envelope protein gp120 plays a major role in binding and budding in the central nervous system (CNS) and impacts dopaminergic functions. However, the mechanisms utilized by HIV-1 clades to exert differential effects and the methamphetamine (METH)-associated dopaminergic dysfunction are poorly understood. We hypothesized that clade B and C gp120 structural sequences, modeling based analysis, dopaminergic effect, and METH potentiate neuronal toxicity in astrocytes. We evaluated the effect of clade B and C gp120 and/or METH on the DRD-2, DAT, CaMKs and CREBP transcription. Both the structural sequence and modeling studies demonstrated that clade B gp120 in V1-V4, α -2 and N-glycosylated sites are distinct from clade C gp120. The distinct structure and sequence variation of clade B gp120 differentially impact DRD-2, DAT, CaMK II and CaMK IV mRNA, protein and intracellular expression compared to clade C gp120. However, CREB transcription is upregulated by both clade B and C gp120, and METH co-treatment potentiated these effects. In conclusion, distinct structural sequences of HIV-1 clade B and C gp120 differentially regulate the dopaminergic pathway and METH potentiates neurotoxicity.

PLOS ONE, 2015

Mild-to-moderate tobacco smoking is highly prevalent in HIV-infected individuals, and is known to... more Mild-to-moderate tobacco smoking is highly prevalent in HIV-infected individuals, and is known to exacerbate HIV pathogenesis. The objective of this study was to determine the specific effects of mild-to-moderate smoking on viral load, cytokine production, and oxidative stress and cytochrome P450 (CYP) pathways in HIV-infected individuals who have not yet received antiretroviral therapy (ART). Thirty-two human subjects were recruited and assigned to four different cohorts as follows: a) HIV negative non-smokers, b) HIV positive non-smokers, c) HIV negative mild-to-moderate smokers, and d) HIV positive mild-to-moderate smokers. Patients were recruited in Cameroon, Africa using strict selection criteria to exclude patients not yet eligible for ART and not receiving conventional or traditional medications. Those with active tuberculosis, hepatitis B or with a history of substance abuse were also excluded. Our results showed an increase in the viral load in the plasma of HIV positive patients who were mild-to-moderate smokers compared to individuals who did not smoke. Furthermore, although we did not observe significant changes in the levels of most pro-inflammatory cytokines, the cytokine IL-8 and MCP-1 showed a significant decrease in the plasma of HIV-infected patients and smokers compared with HIV negative non-smokers. Importantly, HIV-infected individuals and smokers showed a significant increase in oxidative stress compared with HIV negative non-smoker subjects in both plasma and monocytes. To examine the possible pathways involved in increased oxidative stress and viral load, we determined the mRNA levels of several antioxidant and cytochrome P450 enzymes in monocytes. The results showed that the levels of most antioxidants are unaltered, suggesting their inability to counter oxidative stress. While CYP2A6 was induced in smokers, CYP3A4 was induced in HIV and HIV positive smokers compared with HIV negative non-smokers. Overall, the findings suggest a possible association of oxidative stress and perhaps CYP pathway with smoking-mediated increased viral load in HIV positive individuals.

Journal of neuroimmune pharmacology : the official journal of the Society on NeuroImmune Pharmacology, 2009

Marijuana cannabinoids, the endocannabinoids, and cannabinoid cell receptors have been shown to p... more Marijuana cannabinoids, the endocannabinoids, and cannabinoid cell receptors have been shown to play important roles in immune regulation particularly as potent modulators of anti-inflammatory cytokines. The predominant cannabinoid receptor involved in this immune regulation is cannabinoid receptor 2 (CB(2)), which is predominantly expressed in B lymphocytes. However, the promoter region and mechanisms of CB(2) gene regulation are unknown in this immune cell type. Utilizing a combination of bioinformatics, 5' rapid amplification of cDNA ends (5' RACE), real-time reverse transcription-polymerase chain reaction, DNA sequencing, and luciferase reporter assays, we show that human B cells express one CB(2) transcript while mouse B cells express three CB(2) transcripts, with specific transcript selection occurring during B cell activation by lipopolysaccharide. Alignment of our sequenced RACE products to either the mouse or human genome, along with the GenBank submitted mRNA seque...

PLoS ONE, 2014

Arachidonic acid (AA) is known to be increased in HIV infected patients and illicit drug users ar... more Arachidonic acid (AA) is known to be increased in HIV infected patients and illicit drug users are linked with severity of viral replication, disease progression, and impaired immune functions. Studies have shown that cocaine accelerates HIV infection and disease progression mediated by immune cells. Dendritic cells (DC) are the first line of antigen presentation and defense against immune dysfunction. However, the role of cocaine use in HIV associated acceleration of AA secretion and its metabolites on immature dendritic cells (IDC) has not been elucidated yet. The aim of this study is to elucidate the mechanism of AA metabolites cyclooxygenase-2 (COX-2), prostaglandin E2 synthetase (PGE 2 ), thromboxane A2 receptor (TBXA 2 R), cyclopentenone prostaglandins (CyPG), such as 15-deoxy-D12,14-PGJ2

International Journal of Nanomedicine, 2015

Neurochemistry International, 2011

Current HIV Research, 2014

According to a survey from the HIV Cost and Services Utilization Study (HCSUS), approximately 53%... more According to a survey from the HIV Cost and Services Utilization Study (HCSUS), approximately 53% of HIV-infected patients reported drinking alcohol and 8% were classified as heavy drinkers. The role of alcohol as a risk factor for HIV infection has been widely studied and recent research has found a significant association between heavy alcohol consumption and lower levels of CD4 T cells among HIV-infected alcoholics. Although there is evidence on the role of alcohol as a risk factor for HIV transmission and disease progression, there is a need for population studies to determine the genetic mechanisms that affect alcohol's role in HIV disease progression. One of the mechanisms of interest is the dopaminergic system. To date, the effects of dopamine on HIV neuroimmune pathogenesis are not well understood; however, dopaminergic neural degeneration due to HIV is known to occur by viral invasion into the brain via immune cells, and modulation of dopamine in the CNS may be a common mechanism by which different types of substances of abuse impact HIV disease progression. Although previous studies have shown an association of D(2) dopamine receptor (DRD2) polymorphisms with severity of alcohol dependence, the expression of this allele risk on HIV patients with alcohol dependence has not been systematically explored. In the current study, DRD2 Taq1A and C957T SNP genotyping analyses were performed in 165 HIV-infected alcohol abusers and the results were examined with immune status and CD4 counts.

PLoS ONE, 2013

Cocaine and other drugs of abuse increase HIV-induced immunopathogenesis; and neurobiological mec... more Cocaine and other drugs of abuse increase HIV-induced immunopathogenesis; and neurobiological mechanisms of cocaine addiction implicate a key role for microRNAs (miRNAs), single-stranded non-coding RNAs that regulate gene expression and defend against viruses. In fact, HIV defends against miRNAs by actively suppressing the expression of polycistronic miRNA cluster miRNA-17/92, which encodes miRNAs including miR-20a. IFN-g production by natural killer cells is regulated by miR-155 and this miRNA is also critical to dendritic cell (DC) maturation. However, the impact of cocaine on miR-155 expression and subsequent HIV replication is unknown. We examined the impact of cocaine on two miRNAs, miR-20a and miR-155, which are integral to HIV replication, and immune activation. Using miRNA isolation and analysis, RNA interference, quantitative real time PCR, and reporter assays we explored the effects of cocaine on miR-155 and miR-20 in the context of HIV infection. Here we demonstrate using monocyte-derived dendritic cells (MDCCs) that cocaine significantly inhibited miR-155 and miR-20a expression in a dose dependent manner. Cocaine and HIV synergized to lower miR-155 and miR-20a in MDDCs by 90%. Cocaine treatment elevated LTR-mediated transcription and PU.1 levels in MDCCs. But in context of HIV infection, PU.1 was reduced in MDDCs regardless of cocaine presence. Cocaine increased DC-SIGN and and decreased CD83 expression in MDDC, respectively. Overall, we show that cocaine inhibited miR-155 and prevented maturation of MDDCs; potentially, resulting in increased susceptibility to HIV-1. Our findings could lead to the development of novel miRNA-based therapeutic strategies targeting HIV infected cocaine abusers. Citation: Napuri J, Pilakka-Kanthikeel S, Raymond A, Agudelo M, Yndart-Arias A, et al. (2013) Cocaine Enhances HIV-1 Infectivity in Monocyte Derived Dendritic Cells by Suppressing microRNA-155. PLoS ONE 8(12): e83682.

Alcoholism: Clinical and Experimental Research, 2014

This commentary is to highlight the relevance and public interest of the review published by Silv... more This commentary is to highlight the relevance and public interest of the review published by Silverstein and Kumar, which focuses on the mechanisms by which alcohol and HIV-1 infection cause increased in central nervous system (CNS) damage. The overall review is based on previous literature with cell culture systems and animal models that have demonstrated that exposure to alcohol and HIV infection or HIV viral proteins result in synergistic up-regulation of pro-inflammatory cytokines and oxidative stress. The authors discuss the effects of alcohol on cells in the CNS, followed by a brief discussion on the impact of HIV-1 and HIV proteins on the CNS, and the final section focuses on the combined effects of HIV and alcohol on the CNS as determined by in vitro, in vivo, and clinical studies.

PloS one, 2016

Epigenetic mechanisms have been shown to play a role in alcohol use disorders (AUDs) and may prov... more Epigenetic mechanisms have been shown to play a role in alcohol use disorders (AUDs) and may prove to be valuable therapeutic targets. However, the involvement of histone deacetylases (HDACs) on alcohol-induced oxidative stress of human primary monocyte-derived dendritic cells (MDDCs) has not been elucidated. In the current study, we took a novel approach combining ex vivo, in vitro and in silico analyses to elucidate the mechanisms of alcohol-induced oxidative stress and role of HDACs in the periphery. ex vivo and in vitro analyses of alcohol-modulation of class I HDACs and activity by MDDCs from self-reported alcohol users and non-alcohol users was performed. Additionally, MDDCs treated with alcohol were assessed using qRT-PCR, western blot, and fluorometric assay. The functional effects of alcohol-induce oxidative stress were measured in vitro using PCR array and in silico using gene expression network analysis. Our findings show, for the first time, that MDDCs from self-reported...

Frontiers in microbiology, 2015

During human immunodeficiency virus (HIV) infection, alcohol has been known to induce inflammatio... more During human immunodeficiency virus (HIV) infection, alcohol has been known to induce inflammation while cannabinoids have been shown to have an anti-inflammatory role. For instance cannabinoids have been shown to reduce susceptibility to HIV-1 infection and attenuate HIV replication in macrophages. Recently, we demonstrated that alcohol induces cannabinoid receptors and regulates cytokine production by monocyte-derived dendritic cells (MDDC). However, the ability of alcohol and cannabinoids to alter MDDC function during HIV infection has not been clearly elucidated yet. In order to study the potential impact of alcohol and cannabinoids on differentiated MDDC infected with HIV, monocytes were cultured for 7 days with GM-CSF and IL-4, differentiated MDDC were infected with HIV-1Ba-L and treated with EtOH (0.1 and 0.2%), THC (5 and 10 μM), or JWH-015 (5 and 10 μM) for 4-7 days. HIV infection of MDDC was confirmed by p24 and Long Terminal Repeats (LTR) estimation. MDDC endocytosis assa...

Journal of alcoholism and drug dependence, 2015

The role of platelets in the neurological diseases that underlie cognitive impairment has attract... more The role of platelets in the neurological diseases that underlie cognitive impairment has attracted increasing attention in recent years. Multiple pathways in platelets contribute to host defenses, as well as to CNS function. In the current study, we hypothesize that the Blood Brain Barrier (BBB) is disrupted when exposed to platelets from patients with triple Co-morbidity (hazardous alcohol users+ HIV+ thrombocytopenia), compared to those with dual, single or no morbidity (HIV only, alcohol only or healthy controls).

International Journal of Nanomedicine, 2015

In the late nineteenth century, Paul Langerhans discovered Langerhans cells, a form of dendritic ... more In the late nineteenth century, Paul Langerhans discovered Langerhans cells, a form of dendritic cell (DC) found on the skin. However, the term DC was first described in 1973 by Ralph M. Steinman after identifying a population of dendritic-shaped cells in the spleen of mice. Increased research on DC lead to the recognition of DCs as professional antigen presenting cells (APCs). DCs can be classified into different subsets based on their location, marker expression, immune function, and cytokine secretion. To date, four major DC subtypes have been identified: myeloid (mDCs) and plasmacytoid (pDCs) in the blood, follicular dendritic cells (FDCs) in lymph follicles, and Langerhans cells in tissues such as the skin and mucosal epithelial. DCs comprise ≤2% of total peripheral-blood mononuclear cells (PBMCs). However, due to their role in the regulation of the adaptive immune response and their localization, DCs have been recognized as the first line of defense against any pathogen includ...

Journal of Alcoholism & Drug Dependence, 2015

Due to the legalization of marijuana and the increased demand for cannabis and alcohol consumptio... more Due to the legalization of marijuana and the increased demand for cannabis and alcohol consumption, research efforts highlighting the biomedical consequences of the use of alcohol and cannabinoids are not only relevant to the substance abuse scientific field, but are also of public health interest. Moreover, an overview of the recent literature about alcohol and cannabinoids neuro-immunomodulatory effects highlighting their future therapeutic potentials will provide a significant contribution to science and medicine. Therefore, in the current review, we will first discuss briefly the prevalence of alcohol and marijuana abuse, followed by a discussion on the individual effects of alcohol and cannabinoids on the immune system; then, we will focus on the role of endocannabinoids on the alcohol-induced inflammatory effects. In addition, the review also incorporates cytokine array data obtained from human monocyte-derived dendritic cells, providing a different perspective on the alcohol and cannabinoid abuse divergent effects on cytokine production. The final section will highlight the therapeutic potential of cannabinoid receptors and the novel strategies to treat alcohol dependence as determined by in vitro, in vivo and clinical studies.

Frontiers in Microbiology, 2015

ACS chemical neuroscience, Jan 25, 2015

In present research work, for the first time we demonstrated that neuropathogenesis in HIV-1 clad... more In present research work, for the first time we demonstrated that neuropathogenesis in HIV-1 clade B & C infection is associated with IL-33 and ST2 dysregulation i.e., implication towards neuropathogenesis. It is known that neuropathogenesis of HIV infected individuals is clade dependent. Pro-inflammatory cytokines and related receptors played a significant role in the complex regulatory mechanisms of neuropathogenesis in HIV-1 infection. Among them, IL-33 is an inflammatory cytokine expressed in the central nervous system (CNS) activates microglia cells and may affect neuroimmune inflammatory processes involved in HIV neuropathogenesis. Beside this, IL-33 receptor (ST2) plays a role in neuroinflammatory processes through the modulation of the biological action of IL-33. qRT-PCR, ELISA, western blot (WB) and flow cytometry experiments were performed to elucidate the role of IL-33/ST2 in HIV neuropathogenesis in CNS cell. Apoptosis and mechanisms of IL-33 in neuronal cells were studi...

Scientific Reports, 2015

HIV subtypes or clades differentially induce HIV-associated neurocognitive disorders (HAND) and s... more HIV subtypes or clades differentially induce HIV-associated neurocognitive disorders (HAND) and substance abuse is known to accelerate HIV disease progression. The HIV-1 envelope protein gp120 plays a major role in binding and budding in the central nervous system (CNS) and impacts dopaminergic functions. However, the mechanisms utilized by HIV-1 clades to exert differential effects and the methamphetamine (METH)-associated dopaminergic dysfunction are poorly understood. We hypothesized that clade B and C gp120 structural sequences, modeling based analysis, dopaminergic effect, and METH potentiate neuronal toxicity in astrocytes. We evaluated the effect of clade B and C gp120 and/or METH on the DRD-2, DAT, CaMKs and CREBP transcription. Both the structural sequence and modeling studies demonstrated that clade B gp120 in V1-V4, α -2 and N-glycosylated sites are distinct from clade C gp120. The distinct structure and sequence variation of clade B gp120 differentially impact DRD-2, DAT, CaMK II and CaMK IV mRNA, protein and intracellular expression compared to clade C gp120. However, CREB transcription is upregulated by both clade B and C gp120, and METH co-treatment potentiated these effects. In conclusion, distinct structural sequences of HIV-1 clade B and C gp120 differentially regulate the dopaminergic pathway and METH potentiates neurotoxicity.

PLOS ONE, 2015

Mild-to-moderate tobacco smoking is highly prevalent in HIV-infected individuals, and is known to... more Mild-to-moderate tobacco smoking is highly prevalent in HIV-infected individuals, and is known to exacerbate HIV pathogenesis. The objective of this study was to determine the specific effects of mild-to-moderate smoking on viral load, cytokine production, and oxidative stress and cytochrome P450 (CYP) pathways in HIV-infected individuals who have not yet received antiretroviral therapy (ART). Thirty-two human subjects were recruited and assigned to four different cohorts as follows: a) HIV negative non-smokers, b) HIV positive non-smokers, c) HIV negative mild-to-moderate smokers, and d) HIV positive mild-to-moderate smokers. Patients were recruited in Cameroon, Africa using strict selection criteria to exclude patients not yet eligible for ART and not receiving conventional or traditional medications. Those with active tuberculosis, hepatitis B or with a history of substance abuse were also excluded. Our results showed an increase in the viral load in the plasma of HIV positive patients who were mild-to-moderate smokers compared to individuals who did not smoke. Furthermore, although we did not observe significant changes in the levels of most pro-inflammatory cytokines, the cytokine IL-8 and MCP-1 showed a significant decrease in the plasma of HIV-infected patients and smokers compared with HIV negative non-smokers. Importantly, HIV-infected individuals and smokers showed a significant increase in oxidative stress compared with HIV negative non-smoker subjects in both plasma and monocytes. To examine the possible pathways involved in increased oxidative stress and viral load, we determined the mRNA levels of several antioxidant and cytochrome P450 enzymes in monocytes. The results showed that the levels of most antioxidants are unaltered, suggesting their inability to counter oxidative stress. While CYP2A6 was induced in smokers, CYP3A4 was induced in HIV and HIV positive smokers compared with HIV negative non-smokers. Overall, the findings suggest a possible association of oxidative stress and perhaps CYP pathway with smoking-mediated increased viral load in HIV positive individuals.

Journal of neuroimmune pharmacology : the official journal of the Society on NeuroImmune Pharmacology, 2009

Marijuana cannabinoids, the endocannabinoids, and cannabinoid cell receptors have been shown to p... more Marijuana cannabinoids, the endocannabinoids, and cannabinoid cell receptors have been shown to play important roles in immune regulation particularly as potent modulators of anti-inflammatory cytokines. The predominant cannabinoid receptor involved in this immune regulation is cannabinoid receptor 2 (CB(2)), which is predominantly expressed in B lymphocytes. However, the promoter region and mechanisms of CB(2) gene regulation are unknown in this immune cell type. Utilizing a combination of bioinformatics, 5' rapid amplification of cDNA ends (5' RACE), real-time reverse transcription-polymerase chain reaction, DNA sequencing, and luciferase reporter assays, we show that human B cells express one CB(2) transcript while mouse B cells express three CB(2) transcripts, with specific transcript selection occurring during B cell activation by lipopolysaccharide. Alignment of our sequenced RACE products to either the mouse or human genome, along with the GenBank submitted mRNA seque...

PLoS ONE, 2014

Arachidonic acid (AA) is known to be increased in HIV infected patients and illicit drug users ar... more Arachidonic acid (AA) is known to be increased in HIV infected patients and illicit drug users are linked with severity of viral replication, disease progression, and impaired immune functions. Studies have shown that cocaine accelerates HIV infection and disease progression mediated by immune cells. Dendritic cells (DC) are the first line of antigen presentation and defense against immune dysfunction. However, the role of cocaine use in HIV associated acceleration of AA secretion and its metabolites on immature dendritic cells (IDC) has not been elucidated yet. The aim of this study is to elucidate the mechanism of AA metabolites cyclooxygenase-2 (COX-2), prostaglandin E2 synthetase (PGE 2 ), thromboxane A2 receptor (TBXA 2 R), cyclopentenone prostaglandins (CyPG), such as 15-deoxy-D12,14-PGJ2

International Journal of Nanomedicine, 2015

Neurochemistry International, 2011

Current HIV Research, 2014

According to a survey from the HIV Cost and Services Utilization Study (HCSUS), approximately 53%... more According to a survey from the HIV Cost and Services Utilization Study (HCSUS), approximately 53% of HIV-infected patients reported drinking alcohol and 8% were classified as heavy drinkers. The role of alcohol as a risk factor for HIV infection has been widely studied and recent research has found a significant association between heavy alcohol consumption and lower levels of CD4 T cells among HIV-infected alcoholics. Although there is evidence on the role of alcohol as a risk factor for HIV transmission and disease progression, there is a need for population studies to determine the genetic mechanisms that affect alcohol's role in HIV disease progression. One of the mechanisms of interest is the dopaminergic system. To date, the effects of dopamine on HIV neuroimmune pathogenesis are not well understood; however, dopaminergic neural degeneration due to HIV is known to occur by viral invasion into the brain via immune cells, and modulation of dopamine in the CNS may be a common mechanism by which different types of substances of abuse impact HIV disease progression. Although previous studies have shown an association of D(2) dopamine receptor (DRD2) polymorphisms with severity of alcohol dependence, the expression of this allele risk on HIV patients with alcohol dependence has not been systematically explored. In the current study, DRD2 Taq1A and C957T SNP genotyping analyses were performed in 165 HIV-infected alcohol abusers and the results were examined with immune status and CD4 counts.

PLoS ONE, 2013

Cocaine and other drugs of abuse increase HIV-induced immunopathogenesis; and neurobiological mec... more Cocaine and other drugs of abuse increase HIV-induced immunopathogenesis; and neurobiological mechanisms of cocaine addiction implicate a key role for microRNAs (miRNAs), single-stranded non-coding RNAs that regulate gene expression and defend against viruses. In fact, HIV defends against miRNAs by actively suppressing the expression of polycistronic miRNA cluster miRNA-17/92, which encodes miRNAs including miR-20a. IFN-g production by natural killer cells is regulated by miR-155 and this miRNA is also critical to dendritic cell (DC) maturation. However, the impact of cocaine on miR-155 expression and subsequent HIV replication is unknown. We examined the impact of cocaine on two miRNAs, miR-20a and miR-155, which are integral to HIV replication, and immune activation. Using miRNA isolation and analysis, RNA interference, quantitative real time PCR, and reporter assays we explored the effects of cocaine on miR-155 and miR-20 in the context of HIV infection. Here we demonstrate using monocyte-derived dendritic cells (MDCCs) that cocaine significantly inhibited miR-155 and miR-20a expression in a dose dependent manner. Cocaine and HIV synergized to lower miR-155 and miR-20a in MDDCs by 90%. Cocaine treatment elevated LTR-mediated transcription and PU.1 levels in MDCCs. But in context of HIV infection, PU.1 was reduced in MDDCs regardless of cocaine presence. Cocaine increased DC-SIGN and and decreased CD83 expression in MDDC, respectively. Overall, we show that cocaine inhibited miR-155 and prevented maturation of MDDCs; potentially, resulting in increased susceptibility to HIV-1. Our findings could lead to the development of novel miRNA-based therapeutic strategies targeting HIV infected cocaine abusers. Citation: Napuri J, Pilakka-Kanthikeel S, Raymond A, Agudelo M, Yndart-Arias A, et al. (2013) Cocaine Enhances HIV-1 Infectivity in Monocyte Derived Dendritic Cells by Suppressing microRNA-155. PLoS ONE 8(12): e83682.