The U937 macrophage cell line expresses enzymatically active l-Dopa decarboxylase

Kokkinou, Ioanna; Fragoulis, Emmanuel G.; Vassilacopoulou, Dido

doi:10.1016/j.jneuroim.2009.09.001

Cited by 21 publications

(24 citation statements)

References 44 publications

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“…Neural and non-neural promoters have been identified 5' to the flanking region of the respective exon 1 (Le Van Thai et al, 1993;Sumi-Ichinose et al, 1995;Chatelin et al, 2001;Dugast-Darzacq et al, 2004). The generation of the two alternative DDC mRNAs is not a mutually exclusive and tissue-specific event as previously thought (Siaterli et al, 2003;Vassilacopoulou et al, 2004;Kokkinou et al, 2009a;Kokkinou et al, 2009b;Chalatsa et al, 2011).An alternative splicing event has been described within the coding region of DDC mRNA, leading to the formation of a shorter transcript lacking exon 3 (O'Malley et al, 1995;Chang et al, 1996). It must be noted that the above authors did not specify the nature, neural or non-neural, of this shorter transcript.…”

Section: Transcriptionmentioning

confidence: 89%

DDC (dopa decarboxylase (aromatic L-amino acid decarboxylase))

Florou¹,

Scorilas²,

Vassilacopoulou³

et al. 2012

Atlas of Genetics and Cytogenetics in Oncology and Haematology

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Section: Transcriptionmentioning

confidence: 89%

DDC (dopa decarboxylase (aromatic L-amino acid decarboxylase))

Florou¹,

Scorilas²,

Vassilacopoulou³

et al. 2012

Atlas of Genetics and Cytogenetics in Oncology and Haematology

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“…Tyrosine hydroxylase was detected in rodent macrophages [65], human T-cells [17] and human macrophages from arthritic tissue, although not in macrophages from non-arthritic controls [48], while AADC was found in human U937 cells and human T-cells [38,47]. Dopamine production has not been characterized in human macrophages, but low amounts of dopamine are synthesized in rodent macrophages [65,66] and human PBMC [17,40,67], and AADC in U937 cells is enzymatically active [47]. Dopamine uptake in human macrophages has also not been studied, but dopamine has been detected in cytoplasmic vesicles of human U937 cells and in rodent macrophages [66,67].…”

Section: Discussionmentioning

confidence: 99%

“…Dopamine mediates proliferation, quiescence, chemotaxis and cytokine production in different subtypes of human T-cells [20,21,40-43] and also modulates neutrophil migration and apoptosis [44,45]. Expression of DAT, VMAT2 and AADC were detected in human myeloid cells as well as the promyelocytic U937 cell line [46,47]. Tyrosine hydroxylase and VMAT2 have been found in CD163+ human macrophages from arthritic synovial tissue but not in CD163+ cells from non-arthritic controls [48].…”

Section: Introductionmentioning

confidence: 99%

Characterization and function of the human macrophage dopaminergic system: implications for CNS disease and drug abuse

Gaskill

Carvallo

Eugenín

et al. 2012

J Neuroinflammation

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BackgroundPerivascular macrophages and microglia are critical to CNS function. Drugs of abuse increase extracellular dopamine in the CNS, exposing these cells to elevated levels of dopamine. In rodent macrophages and human T-cells, dopamine was shown to modulate cellular functions through activation of dopamine receptors and other dopaminergic proteins. The expression of these proteins and the effects of dopamine on human macrophage functions had not been studied.MethodsTo study dopaminergic gene expression, qRT-PCR was performed on mRNA from primary human monocyte derived macrophages (MDM). Expression and localization of dopaminergic proteins was examined by immunoblotting isolated plasma membrane, total membrane and cytosolic proteins from MDM. To characterize dopamine-mediated changes in cytokine production in basal and inflammatory conditions, macrophages were treated with different concentrations of dopamine in the presence or absence of LPS and cytokine production was assayed by ELISA. Statistical significance was determined using two-tailed Students’ T-tests or Wilcoxen Signed Rank tests.ResultsThese data show that MDM express mRNA for all five subtypes of dopamine receptors, and that dopamine receptors 3 and 4 are expressed on the plasma membrane. MDM also express mRNA for the dopamine transporter (DAT), vesicular monoamine transporter 2 (VMAT2), tyrosine hydroxylase (TH) and aromatic amino acid decarboxylase (AADC). DAT is expressed on the plasma membrane, VMAT2 on cellular membranes and TH and AADC are in the cytosol. Dopamine also alters macrophage cytokine production in both untreated and LPS-treated cells. Untreated macrophages show dopamine mediated increases IL-6 and CCL2. Macrophages treated with LPS show increased IL-6, CCL2, CXCL8 and IL-10 and decreased TNF-α.ConclusionsMonocyte derived macrophages express dopamine receptors and other dopaminergic proteins through which dopamine may modulate macrophage functions. Thus, increased CNS dopamine levels due to drug abuse may exacerbate the development of neurological diseases including Alzheimer’s disease and HIV associated neurological disorders.

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“…Another study also found D1R in human macrophages (Liang et al 2008). One report in human promyelocytic U937 cells showed enzymatically active AADC (Kokkinou et al 2009), while another found TH and VMAT2 in LPS stimulated U937 cells but not in LPS stimulated THP-1 cells (Capellino et al 2010). The second study also showed TH and VMAT2 in CD163+ macrophages from arthritic but not normal tissues.…”

Section: Dopamine and Hiv In Monocytes And Macrophagesmentioning

confidence: 99%

Drug Induced Increases in CNS Dopamine Alter Monocyte, Macrophage and T Cell Functions: Implications for HAND

Gaskill

Calderon

Coley

et al. 2013

J Neuroimmune Pharmacol

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Central nervous system (CNS) complications resulting from HIV infection remain a major public health problem as individuals live longer due to the success of combined antiretroviral therapy (cART). As many as 70% of HIV infected people have HIV associated neurocognitive disorders (HAND). Many HIV infected individuals abuse drugs, such as cocaine, heroin or methamphetamine, that may be important cofactors in the development of HIV CNS disease. Despite different mechanisms of action, all drugs of abuse increase extracellular dopamine in the CNS. The effects of dopamine on HIV neuropathogenesis are not well understood, and drug induced increases in CNS dopamine may be a common mechanism by which different types of drugs of abuse impact the development of HAND. Monocytes and macrophages are central to HIV infection of the CNS and to HAND. While T cells have not been shown to be a major factor in HIV-associated neuropathogenesis, studies indicate that T cells may play a larger role in the development of HAND in HIV infected drug abusers. Drug induced increases in CNS dopamine may dysregulate functions of, or increase HIV infection in, monocytes, macrophages and T cells in the brain. Thus, characterizing the effects of dopamine on these cells is important for understanding the mechanisms that mediate the development of HAND in drug abusers.

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The U937 macrophage cell line expresses enzymatically active l-Dopa decarboxylase

Cited by 21 publications

References 44 publications

DDC (dopa decarboxylase (aromatic L-amino acid decarboxylase))

DDC (dopa decarboxylase (aromatic L-amino acid decarboxylase))

Characterization and function of the human macrophage dopaminergic system: implications for CNS disease and drug abuse

Drug Induced Increases in CNS Dopamine Alter Monocyte, Macrophage and T Cell Functions: Implications for HAND

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