Expression of substance P, neurokinin-1 receptor and immune markers in the brains of individuals with HIV-associated neuropathology

Spitsin, Sergei; Stevens, Kathleen; Douglas, Steven D.

doi:10.1016/j.jns.2013.07.008

Cited by 11 publications

(9 citation statements)

References 53 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…The expression of HIV receptor (CD4) and chemokine coreceptors (CCR5 and CXCR4) was determined using real-time PCR (57). Total RNA was treated with RNAse free DNAse (Ambion/Life Technologies, Grand Island, NY) and reverse transcribed (1μg) using an AffinityScript qPCR cDNA synthesis kit (Agilent, Santa Clara, CA) with random primer, all as instructed by the manufacturer.…”

Section: Methodsmentioning

confidence: 99%

See 1 more Smart Citation

The Selective Serotonin Reuptake Inhibitor Citalopram Decreases Human Immunodeficiency Virus Receptor and Coreceptor Expression in Immune Cells

Greeson

Gettes

Spitsin

et al. 2016

Biological Psychiatry

Self Cite

View full text Add to dashboard Cite

Background This study investigated whether a selective serotonin reuptake inhibitor (SSRI), citalopram, downregulates the expression of HIV receptor (CD4) and coreceptors (CCR5 and CXCR4) on peripheral blood mononuclear cells (PBMC) and macrophages ex vivo as a potential mechanism of reducing susceptibility to HIV infection. Methods The sample included 150 participants ages 18–58 (59% women, 65% African American, 61% depressed). Monocyte depleted PBMC were treated with phytohemagglutinin (PHA) for 72-hours and then cultured in the presence of IL-2 with vehicle control or SSRI (10−6 M) for 2-hours. To generate monocyte derived macrophages (MDM), monocytes were cultured for 7-days, after which either vehicle control or SSRI (10−6 M) was added for 2-hours. RNA was then collected from both cell types, and CD4, CCR5 and CXCR4 mRNA expression was measured by real-time PCR. Results In PBMC, SSRI treatment decreased expression of CD4 (p=.009), CCR5 (p=.008), and CXCR4 (p<.0001). In MDM, SSRI decreased expression of CD4 (p<.0001) and CXCR4 (p=.0003), but not CCR5 (p=.71). The suppressive effects of SSRI on receptor expression did not differ as a function of depression diagnosis or depressive symptom severity. Conclusions SSRI treatment at a physiologic dose decreased CD4, CCR5 and CXCR4 expression on PBMC and macrophages ex vivo. These findings suggest that SSRI treatment, independent of depression status, downregulates HIV receptor and coreceptor expression and thus may reduce susceptibility of immune cells to HIV infection and decrease inflammation. If clinical trials confirm the present findings, ultimately there may be a role for using SSRI treatment adjunctively in HIV/AIDS.

show abstract

Section: Methodsmentioning

confidence: 99%

“…One-tenth of the resulting cDNA was used as a template for real-time PCR amplification using MyiQ iCycler system (Bio-Rad Laboratories, Inc., Hercules, CA). The sequences of the primers and probes used in this study are listed (57). All primers and probes were synthesized by Integrated DNA Technologies, Inc. (Coralville, IA).…”

Section: Methodsmentioning

confidence: 99%

The Selective Serotonin Reuptake Inhibitor Citalopram Decreases Human Immunodeficiency Virus Receptor and Coreceptor Expression in Immune Cells

Greeson

Gettes

Spitsin

et al. 2016

Biological Psychiatry

Self Cite

View full text Add to dashboard Cite

show abstract

“…The sequences of the primers and probes for GAPDH and HIV-GAG (Integrated DNA Technologies, Coralville, IA, USA) were reported previously [34,35]. For experiments involving detection of viral LTR, HIV stock was treated with DNase (50 g/ml) for 30 min before infection.…”

Section: Rna Extraction and Real-time Rt-pcr Assaysmentioning

confidence: 99%

HIV infection of macrophages is enhanced in the presence of increased expression of CD163 induced by substance P

Tuluc

Meshki²,

Spitsin³

et al. 2014

Journal of Leukocyte Biology

Self Cite

View full text Add to dashboard Cite

Activation of NK1R by SP contributes to increased HIV-1 infection in macrophages. The scavenger receptor CD163 is expressed on cells of monocyte-macrophage origin. Our main goal was to determine if there is interplay among SP, CD163 expression, and HIV infection in macrophages. We showed that SP triggers intracellular calcium elevation and increased CD163 expression in human monocytes in a time- and concentration-dependent manner. The role of CD163 on HIV infection was examined by RT-PCR in sorted monocytes (CD163(low) and CD163(high)) and in macrophages having CD163 knocked down using siRNA. We found that the productivity of HIV infection was higher in CD163(high) cells. Additionally, in macrophages with CD163 expression knocked down, we found a significant decrease of HIV infection. Furthermore, Hb-Hp complexes, which function as an endogenous ligand for CD163, decreased HIV infection in macrophages in a dose-dependent manner. Thus, we demonstrate that SP induces higher levels of CD163 in monocytes and that high expression of CD163 is associated with increases HIV infection in macrophages. Thus, in addition to being a prognostic marker of HIV infection, the expression of CD163 on macrophages may be critical in HIV immunopathogenesis.

show abstract

“…HIV infection is accompanied by a higher concentration and faster synthesis of positive acute phase proteins, but not by lower concentrations and slower synthesis of negative acute phase proteins 62 . For example, the positive acute phase proteins haptoglobin and haptoglobin-hemoglobin scavenger receptor CD163 levels in HIV-infected patients are positively correlated with viral load 63 , and with the progression of HIV-infection 64 . Likewise, ceruloplasmin is increased in HIV infected patients 65 , in association with cognitive impairment 66 , and with decreased oxidative damage in untreated HIV-positive subjects 67 .…”

Section: Discussionmentioning

confidence: 99%

Modifications in acute phase and complement systems predict shifts in cognitive status of HIV-infected patients

Ubaida‐Mohien

Lamberty

Dickens

et al. 2017

Aids

View full text Add to dashboard Cite

The prevalence of HIV-Associated Neurocognitive Disorders (HAND) has not changed considerably in the last two decades. Potent antiretroviral therapy (ART) has shifted the severity of HAND to milder phenotypes, but excess morbidity and mortality continue to be associated with HAND. Changes in numerous markers of immune function, inflammation and cellular stress have been repeatedly associated with HAND but the underlying systems that drive these changes have not been identified. In this study we used systems informatics to interrogate the CSF proteomic content of longitudinal samples obtained from HIV-infected adults with stably unimpaired, stably impaired, worsening, or improving neurocognitive (NC) performance. The patterns of change in CSF protein content implicated the induction of acute phase and complement systems as important regulators of NC status. Worsening NC performance was preceded by induction of acute phase and complement systems, while improving NC performance was preceded by a downregulation of these systems.

show abstract

Expression of substance P, neurokinin-1 receptor and immune markers in the brains of individuals with HIV-associated neuropathology

Cited by 11 publications

References 53 publications

The Selective Serotonin Reuptake Inhibitor Citalopram Decreases Human Immunodeficiency Virus Receptor and Coreceptor Expression in Immune Cells

The Selective Serotonin Reuptake Inhibitor Citalopram Decreases Human Immunodeficiency Virus Receptor and Coreceptor Expression in Immune Cells

HIV infection of macrophages is enhanced in the presence of increased expression of CD163 induced by substance P

Modifications in acute phase and complement systems predict shifts in cognitive status of HIV-infected patients

Contact Info

Product

Resources

About