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Wen-Zhe Ho

Publications and source records attributed to Wen-Zhe Ho.

32 records · Page 2Linked to original sources
PubMed2003

Morphine enhances hepatitis C virus (HCV) replicon expression.

Little information is available regarding whether substance abuse enhances hepatitis C virus (HCV) replication and promotes HCV disease progression. We investigated whether morphine alters HCV mRNA expression in HCV replicon-containing liver cells. Morphine significantly increased HCV mRNA expression, an effect which could be abolished by either of the opioid receptor antagonists, naltrexone or beta-funaltrexamine. Investigation of the mechanism responsible for this enhancement of HCV replicon expression demonstrated that morphine activated NF-kappaB promoter and that caffeic acid phenethyl ester, a specific inhibitor of the activation of NF-kappaB, blocked morphine-activated HCV RNA expression. In addition, morphine compromised the anti-HCV effect of interferon alpha (IFN-alpha). Our in vitro data indicate that morphine may play an important role as a positive regulator of HCV replication in human hepatic cells and may compromise IFN-alpha therapy.

Antiviral Agents↗
PubMed2003

Interleukin-1beta stimulates macrophage inflammatory protein-1alpha and -1beta expression in human neuronal cells (NT2-N).

Chemokines are important mediators in immune responses and inflammatory processes of neuroimmunologic and infectious diseases. Although chemokines are expressed predominantly by cells of the immune system, neurons also express chemokines and chemokine receptors. We report herein that human neuronal cells (NT2-N) produce macrophage inflammatory protein-1alpha and -1beta (MIP-1alpha and MIP-1beta), which could be enhanced by interleukin (IL)-1beta at both mRNA and protein levels. The addition of supernatants from human peripheral blood monocyte-derived macrophage (MDM) cultures induced MIP-1beta mRNA expression in NT2-N cells. Anti-IL-1beta antibody removed most, but not all, of the MDM culture supernatant-induced MIP-1beta mRNA expression in NT2-N cells, suggesting that IL-1beta in the MDM culture supernatants is a major factor in the induction of MIP-1beta expression. Investigation of the mechanism(s) responsible for IL-1beta-induced MIP-1alpha and -1beta expression demonstrated that IL-1beta activated nuclear factor kappa B (NF-kappaB) promoter-directed luciferase activity in NT2-N cells. Caffeic acid phenethyl ester, a potent and specific inhibitor of activation of NF-kappaB, not only blocked IL-1beta-induced activation of the NF-kappaB promoter but also decreased IL-1beta-induced MIP-1alpha and -1beta expression in NT2-N cells. These data suggest that NF-kappaB is at least partially involved in the IL-1beta-mediated action on MIP-1alpha and -1beta in NT2-N cells. IL-1beta-mediated up-regulation of beta-chemokine expression may have important implications in the immunopathogenesis of inflammatory diseases in the CNS.

Cell Line↗
PubMed2003

Alcohol potentiates hepatitis C virus replicon expression.

Alcohol consumption accelerates liver damage and diminishes the anti-hepatitis C virus (HCV) effect of interferon alfa (IFN-alpha) in patients with HCV infection. It is unknown, however, whether alcohol enhances HCV replication and promotes HCV disease progression. The availability of the HCV replicon containing hepatic cells has provided a unique opportunity to investigate the interaction between alcohol and HCV replicon expression. We determined whether alcohol enhances HCV RNA expression in the replicon containing hepatic cells. Alcohol, in a concentration-dependent fashion, significantly increased HCV replicon expression. Alcohol also compromised the anti-HCV effect of IFN-alpha. Investigation of the mechanism(s) responsible for the alcohol action on HCV replicon indicated that alcohol activated nuclear factor kappaB (NF-kappaB) promoter. Caffeic acid phenethyl ester (CAPE), a specific inhibitor of the activation of NF-kappaB, abolished alcohol-induced HCV RNA expression. In addition, naltrexone, an opiate receptor antagonist, abrogated the enhancing effect of alcohol on HCV replicon expression. In conclusion, alcohol, probably through the activation of NF-kappaB and the endogenous opioid system, enhances HCV replicon expression and compromises the anti-HCV effect of IFN-alpha. Thus, alcohol may play an important role in vivo as a cofactor in HCV disease progression and compromise IFN-alpha-based therapy against HCV infection.

Antidotes↗
PubMed2003

Quantification of CCR5 mRNA in human lymphocytes and macrophages by real-time reverse transcriptase PCR assay.

CCR5, a beta-chemokine receptor, plays an important role in human immunodeficiency virus (HIV) infection of human immune cells, as it is a primary coreceptor for HIV entry into macrophages. We have applied a newly developed real-time reverse transcriptase PCR (RT-PCR) assay for the quantification of CCR5 mRNA in human blood immune cells. The CCR5 real-time RT-PCR assay has a sensitivity of 100 mRNA copies, with a dynamic range of detection between 10(2) and 10(6) copies of the CCR5 mRNA transcripts per reaction. The assay is highly reproducible, with an intra-assay coefficient of variation of the threshold cycle of less than 2.07%. When used for quantification of CCR5 mRNA in human monocyte-derived macrophages (MDM) and peripheral blood lymphocytes (PBL), the assay has precision and reproducibility. MDM expressed higher levels of CCR5 mRNA than did PBL. Thus, this assay has the potential and a wide application for the investigation of the role of CCR5 in inflammatory diseases and viral infections, including HIV disease.

Blood Cells↗
PubMed2002

A non-peptide substance P antagonist down-regulates SP mRNA expression in human mononuclear phagocytes.

Substance P (SP), a potent modulator of neuroimmunoregulation, exerts its activity by binding to the neurokinin-1 receptor (NK-1R). The SP-NK-1R interaction is important in inflammation and viral infections, including HIV infection of human immune cells. We recently demonstrated that SP modulates HIV replication and that a non-peptide SP antagonist CP-96,345 inhibits HIV replication in human monocyte-derived macrophages (MDM) by affecting the SP-NK-1R interaction. In order to examine the effect of the SP antagonist on SP mRNA expression, MDM was incubated with or without CP-96,345 in the presence or absence of HIV infection. SP mRNA expression in these cells was then determined by real-time PCR technology. The effect of CP-96,345 on chemokine gene expression was also investigated by using a cDNA array assay. CP-96,345 down-regulated SP mRNA expression and antagonized exogenous SP-enhanced SP expression at the mRNA level, suggesting that SP autocrine regulation was interrupted by CP-96,345. CP-96,345 inhibited HIV replication in MDM, associated with down-regulated SP mRNA expression in comparison to HIV infection controls. In parallel with down-regulated SP and CCR5 mRNA expression, cDNA array assays indicated that CP-96,345 treatment also inhibited IL-8 gene expression, while enhancing expression of fractalkine and monocyte chemotactic protein-3 (MCP-3). Since SP plays an important role in inflammation and viral infections, these studies may have potential applications for therapeutic intervention of inflammation and viral infection of immune cells.

Anti-Inflammatory Agents, Non-Steroidal↗
PubMed2002

Substance P and Human Immunodeficiency Virus Infection: Psychoneuroimmunology.

Effects on the immune system caused by changes in behavioral state or brain activity are mediated, at least in part, through neuroendocrine-immune pathways. Life stress and depression may be associated with altered blood levels of central nervous system-released neuropeptides, including substance P (SP). SP acts as a neuroregulator or neurotransmitter in the conduction of nociceptive stimuli, and is a modulator of neuroimmunoregulation. This review summarizes current knowledge regarding the role of the neuropeptide, SP, in psychoneuroimmunology, in particular as it relates to human immunodeficiency virus infection and acquired immunodeficiency disease syndrome. The association between depression, anxiety, and stress in HIV-disease progression suggests that neurobiologic and neurophysiologic factors play a role in modulating HIV infection and responses to antiretroviral therapy. Individuals with HIV or AIDS may experience stressful life circumstances that can result in increased symptoms of anxiety, stress, and/or depression. Furthermore, psychological and psychiatric symptoms, which occur in individuals with HIV and AIDS, may be related to the progression of AIDS disease. This review presents evidence from the literature, as well as findings from basic investigations conducted in the authors' laboratories, demonstrating that SP may play an important role in HIV pathophysiology. SP can impact the susceptibility of immune cells to HIV infection and modulate immune cell functions in ways that may affect the course of HIV in infected individuals. Moreover, modulation of SP activity and SP receptor is being explored for its potential as a novel therapeutic approach to the treatment of some psychological and psychiatric disorders and to the design of new anti-HIV therapy.

Journal Article↗
PubMed2002

HIV enhances substance P expression in human immune cells.

Substance P (SP), a potent modulator of neuroimmunoregulation, is expressed in human immune cells. We observed elevated plasma SP levels in HIV-infected men compared with uninfected subjects. In the present study, we investigated the possible cellular source of the increased SP level caused by HIV infection. Using real-time reverse transcriptase-polymerase chain reaction, we demonstrated that monocyte-derived macrophages (MDM) and lymphocytes from both placental cord blood and adult peripheral blood expressed SP mRNA, which was significantly increased by HIV infection. HIV-induced SP expression was positively related to virus replication in the infected MDM. Purified recombinant HIV envelope glycoprotein 120 (gp120) derived from both the macrophage-tropic strain (MN) and the T lymphocyte-tropic strain (IIIB), when added to MDM cultures, enhanced SP mRNA expression. The gp120-induced SP expression was abrogated by pretreating the cells with soluble CD4. Furthermore, the activation of HIV in the latently infected promonocytic cell line (U1) and T-cell line (ACH-2) up-regulated SP mRNA expression. These data support the hypothesis that interaction of HIV and SP may have significant in vivo relevance to the immunopathogenesis of HIV infection and AIDS.

Blood↗
PubMed2002

Alcohol potentiates HIV-1 infection of human blood mononuclear phagocytes.

BACKGROUND: Acute and chronic alcohol abuse impairs various functions of the immune system and thus has been implicated as a cofactor in HIV infection. The mechanisms by which alcohol affects the function of human immune cells that are the targets for HIV are unknown. METHODS: Human blood monocyte-derived macrophages (MDM) were incubated with or without alcohol (10-40 mM) for 24 hr and then infected with HIV for 24 hr. Culture supernatants were harvested for HIV reverse transcription assay. HIV entry receptor (CCR5, CD4, and CXCR4) expression was determined by reverse transcription-polymerase chain reaction and flow cytometry assays. Beta-chemokines were analyzed using enzyme-linked immunosorbent assay. Different HIV strains (Bal, SF-162, 89.6, and UG024) were used for infection experiments. In addition, ADA (macrophage-tropic strain) and murine leukemia virus envelope-pseudotyped HIV infection was carried out. RESULTS: Although alcohol had little effect on HIV T-lymphocyte-tropic strain infection, it significantly enhanced HIV R5 strain infection in MDM. The enhancing effect of alcohol on the HIV R5 strain was further evidenced by the observation that the R5 (ADA) strain envelope-pseudotyped HIV infection is markedly increased by alcohol, whereas murine leukemia virus envelope-pseudotyped HIV infection was not affected. Alcohol significantly up-regulated CCR5 receptor expression and inhibited the endogenous production of beta-chemokines by MDM. CONCLUSION: Alcohol, through the down-regulation of beta-chemokine production and the up-regulation of CCR5 receptor expression, enhances HIV R5 strain infection of MDM and may have an important role as a cofactor in the progression of HIV disease.

Cells, Cultured↗
PubMed2002

Quantification of substance p mRNA in human immune cells by real-time reverse transcriptase PCR assay.

We have applied a newly developed real-time reverse transcriptase (RT) PCR (RT-PCR) assay for quantification of substance P (SP) mRNA expression (the SP real-time RT-PCR assay) in human blood monocyte-derived macrophages, peripheral blood lymphocytes, and microglia isolated from fetal brain. The SP real-time RT-PCR assay had a sensitivity of 60 mRNA copies, with a dynamic range of detection between 60 and 600,000 copies of the SP gene transcript per reaction mixture. The coefficient of variation of the threshold cycle number between the SP real-time RT-PCR assays was less than 1.16%. This assay with an SP-specific primer pair efficiently recognizes all four isoforms of preprotachykinin A (the SP precursor) gene transcripts. In order to use this assay to measure the levels of SP mRNA in the human immune cells quantitatively, we designed a specific probe (molecular beacon) derived from exon 3 of the SP gene. We demonstrated that the real-time RT-PCR quantitatively detected SP mRNA in the human immune cells, among which the microglia isolated from fetal brain had the highest levels of SP mRNA. The SP real-time PCR assay yielded reproducible data, as the intra-assay variation was less than 1%. Thus, it is feasible to apply the real-time RT-PCR assay for quantification of SP mRNA levels in human immune cells, as well as in other nonneuronal cells. Since SP is a major modulator of neuroimmunoregulation, this assay has the potential for widespread application for basic and clinical investigations.

Adult↗
PubMed2002

Morphine enhances HIV infection of human blood mononuclear phagocytes through modulation of beta-chemokines and CCR5 receptor.

BACKGROUND: Injection drug use remains a significant risk for acquiring HIV infection. The mechanisms by which morphine enhances HIV infection of human immune cells are largely unknown. OBJECTIVE: In this study, we sought to determine the possible mechanisms by which morphine upregulates HIV infection of human blood monocyte-derived macrophages (MDM). METHODS: In this study, MDM were infected with the R5, X4, and R5X4 HIV strains. HIV replication was determined by performing reverse transcriptase activity assays. HIV receptors were determined by performing reverse transcriptase polymerase chain reactions and flow cytometry assays. beta-chemokines were analyzed by performing enzyme-linked immunosorbent assays. In addition, HIV R5 strain and murine leukemia virus envelope-pseudotyped HIV infection was performed to determine whether morphine affects HIV infection of macrophages at entry level. RESULTS: Morphine significantly enhanced HIV R5 strain infection of MDM but had little effect on X4 strain infection. The macrophage-tropic R5 strain envelope-pseudotyped HIV infection was markedly increased by morphine, whereas murine leukemia virus envelope-pseudotyped HIV infection was not significantly affected. Furthermore, morphine significantly upregulated CCR5 receptor expression and inhibited the endogenous production of beta-chemokines in MDM. The opioid receptor antagonist naltrexone blocked the effects of morphine on the production of beta-chemokines. CONCLUSION: Opiates enhance HIV R5 strain infection of macrophages through the downregulation of beta-chemokine production and upregulation of CCR5 receptor expression and may have an important role in HIV immunopathogenesis.

Chemokines, CC↗
PubMed2001

Methadone enhances human immunodeficiency virus infection of human immune cells.

Opiate abuse has been postulated to be a cofactor in the immunopathogenesis of acquired immunodeficiency syndrome (AIDS). This study evaluated whether methadone, a drug widely prescribed for the treatment of drug abusers with opioid dependence, affects human immunodeficiency virus (HIV) infection of human immune cells. When added to human fetal microglia and blood monocyte-derived macrophage cultures, methadone significantly enhanced HIV infection of these cells. This enhancement was associated with the up-regulation of expression of CCR5, a primary coreceptor for macrophage-tropic HIV entry into macrophages. Most importantly, the addition of methadone to the cultures of latently infected peripheral blood mononuclear cells from HIV-infected patients enhanced viral activation and replication. Although the in vivo relevance of these findings remains to be determined, the data underscore the necessity of further studies to define the role of opioids, including methadone, in the immunopathogenesis of HIV infection and AIDS.

Adult↗
PubMedDate not supplied

Drug abuse, innate immunity and hepatitis C virus.

Since its discovery in 1989, hepatitis C virus (HCV) has become a major public health problem. HCV chronically infects an estimated 170 million people worldwide. The seroprevalence of anti-HCV antibody in the United States has been estimated at 1.8%, which corresponds to approximately 4 million people. HCV is the most common chronic blood borne infection in the United States, and the leading cause of liver transplantation in developed countries. Injection drug use is the dominant mode of HCV transmission and accounts for up to 90% of current infections. Opiates and other drug abuse, such as alcohol, have been implicated as cofactors in the pathogenesis of HCV disease. Injection drug use has been the most common risk factor identified in alcoholics with HCV infection. Both opiates and alcohol contribute significantly to morbidity and mortality from HCV disease. These drugs most likely act synergistically to promote the development and progression of HCV disease. However, there is limited information available concerning the interaction of the drug abuse with the host cell innate immunity against HCV infection, which is a major barrier to fundamental understanding of the immunopathogenesis of HCV disease. Therefore, defining the role of the drug abuse in the development of chronic HCV infection is of crucial importance and should provide practical guidance toward the reduction of risk factors that interfere with therapeutic approaches for HCV infection and disease. This review paper focuses on the interplay between drug abuse (opiates and alcohol), innate immunity and HCV in the context of the development of HCV disease.

Alcoholism↗