Expression of somatostatin, cortistatin, and somatostatin receptors in human monocytes, macrophages, and dendritic cells

2003 ◽  
Vol 285 (2) ◽  
pp. E344-E353 ◽  
Author(s):  
Virgil A. S. H. Dalm ◽  
P. Martin van Hagen ◽  
Peter M. van Koetsveld ◽  
Sam Achilefu ◽  
Adriaan B. Houtsmuller ◽  
...  
Keyword(s):  
Dendritic Cells ◽  
Mrna Expression ◽  
Immune Cell ◽  
Rank Order ◽  
Somatostatin Receptors ◽  
Human Monocyte ◽  
Time Dependent ◽  
Mrna Levels ◽  
Human Monocytes ◽  
Activated State

Increasing evidence suggests that neuropeptides play a role in the regulatory mechanisms between the neuroendocrine and immune systems. A differential expression of the five known somatostatin (SS) receptors (sst1–5) has been demonstrated in human immune cells and tissues. However, little is known concerning regulation and expression of sst1–5and the peptide SS. Therefore, we investigated the expression and the time-dependent regulation of sst1–5, SS, and cortistatin (CST), a novel SS-like peptide, in human monocytes (MO), monocyte-derived macrophages (MP), and dendritic cells (DC) in the basal and lipopolysaccharide (LPS)-activated state. MO, MP, and DC selectively expressed sst2mRNA. SS mRNA was not detectable, whereas all samples expressed CST mRNA. Expression levels of sst2and CST mRNA showed marked differences and were in the rank order of MP>>DC>>>MO. LPS stimulation did not induce expression of SS or sst1,3,4,5. However, sst2mRNA expression was upregulated significantly by stimulation with LPS. CST mRNA was upregulated as well. During differentiation of MO in MP or DC, time-dependent, significantly increasing sst2and CST mRNA levels were found. By confocal microscopy, the presence of sst2receptors was demonstrated on MP, but not on DC. This study demonstrates for the first time a selective and inducible expression of the recently discovered CST, as well as sst2, in human monocyte-derived cells, suggesting a role for a CST-sst2system rather than a SS-sst2system in these immune cell types.

scholarly journals Activation of Human Dendritic Cells Is Modulated by Components of the Outer Membranes of Neisseria meningitidis

2003 ◽  
Vol 71 (10) ◽  
pp. 5590-5597 ◽  
Author(s):  
Tamara Al-Bader ◽  
Myron Christodoulides ◽  
John E. Heckels ◽  
Judith Holloway ◽  
Amanda E. Semper ◽  
...  
Keyword(s):  
T Cells ◽  
Dendritic Cells ◽  
Neisseria Meningitidis ◽  
Mrna Expression ◽  
Mhc Class Ii ◽  
Human Monocyte ◽  
Class Ii ◽  
Effective Vaccine ◽  
Tlr4 Mrna ◽  
Mhc Class Ii Molecules

ABSTRACT Neisseria meningitidis serogroup B is a major cause of life-threatening meningitis and septicemia worldwide, and no effective vaccine is available. Initiation of innate and acquired immune responses to N. meningitidis is likely to be dependent on cellular responses of dendritic cells (DC) to antigens present in the outer membrane (OM) of the meningococcus. In this study, the responses of human monocyte-derived DC (mo-DC) to OM isolated from parent (lipopolysaccharide [LPS]-replete) meningococci and from a mutant deficient in LPS were investigated. Parent OM selectively up-regulated Toll-like receptor 4 (TLR4) mRNA expression and induced mo-DC maturation, as reflected by increased production of chemokines, proinflammatory cytokines, and CD83, CD80, CD86, CD40, and major histocompatibility complex (MHC) class II molecules. In contrast, LPS-deficient OM selectively up-regulated TLR2 mRNA expression and induced moderate increases in both cytokine production and expression of CD86 and MHC class II molecules. Preexposure to OM, with or without LPS, augmented the allostimulatory properties of mo-DC, which induced proliferation of naive CD4+ CD45RA+ T cells. In addition, LPS-replete OM induced a greater gamma interferon/interleukin-13 ratio in naive T cells, whereas LPS-deficient OM induced the reverse profile. These data demonstrate that components of the OM, other than LPS, are also likely to be involved in determining the levels of DC activation and the nature of the T-helper immune response.

scholarly journals Functional Modification of Pituitary Somatotropes in the Aromatase Knockout Mouse and the Effect of Estrogen Replacement

Endocrinology ◽  
2004 ◽  
Vol 145 (2) ◽  
pp. 604-612 ◽  
Author(s):  
Ming Yan ◽  
Margaret E. E. Jones ◽  
Maria Hernandez ◽  
Dongling Liu ◽  
Evan R. Simpson ◽  
...  
Keyword(s):  
Mrna Expression ◽  
Molecular Mechanisms ◽  
Somatostatin Receptors ◽  
Mrna Levels ◽  
Gene Encoding ◽  
Gh Secretion ◽  
Ghrh Receptor ◽  
Elevated Expression ◽  
Cyp19 Gene

Abstract Available data on the influence of estradiol (E2) on GH levels remains controversial. A factor contributing to this uncertainty is a lack of knowledge of both E2 action on somatotropes as well as the molecular mechanisms involved. In this study we investigated gene expression implicated in GH secretion in somatotropes derived from female aromatase knockout (ArKO) mice. In these mice E2 production is blocked due to disruption of the Cyp19 gene encoding aromatase, the enzyme responsible for estrogen biosynthesis. The effect of E2 replacement was also studied by in vivo treatment of mice with E2 for 3 wk. It was demonstrated that somatotropes from ArKO mice had a low expression of GH, GH secretagogue receptor, GHRH receptor (GHRH-R), and pituitary-specific transcription factor (Pit-1). On the other hand, the somatotropes exhibited elevated expression of somatostatin receptors (sst1–5). Overall, these effects resulted in a reduction in GH secretion. E2 replacement increased GHRH-R, Pit-1, and GH mRNA levels to 185%, 193%, and 157% and reduced the levels of sst1, sst2, sst4, and sst5 mRNA expression in ArKO mice, respectively. E2 replacement did not affect the levels of pituitary estrogen (α and β) and androgen receptor mRNA expression. It is concluded that the expression of important genes involved in GH synthesis in somatotropes of the female ArKO mouse are functionally down-regulated, and such a down-regulation is reversed to normal levels by E2 replacement. The levels of GH secretagogue receptor, GHRH-R, and Pit-1 mRNA expression were also reduced, and sst1 and sst3 mRNA expression enhanced in aging ArKO and wild-type mice, resulting in a decrease in GH mRNA expression. It is suggested that aging is another important impact factor for the pituitary expression and regulation of GH mRNA in female mice.

99 Effects of Combined TLR Stimulation on Interleukin-27 mRNA Expression in Human Monocyte-derived Dendritic Cells

Cytokine ◽  
2007 ◽  
Vol 39 (1) ◽  
pp. 27
Author(s):  
Claudius U. Meyer ◽  
Doreen Krumbiegel ◽  
Helena Markus ◽  
Michaela Fuidl ◽  
Fred Zepp
Keyword(s):  
Dendritic Cells ◽  
Mrna Expression ◽  
Human Monocyte ◽  
Interleukin 27

scholarly journals Macrophage colony-stimulating factor and granulocyte-macrophage colony- stimulating factor stimulate the synthesis of plasminogen-activator inhibitors by human monocytes

Blood ◽  
1993 ◽  
Vol 82 (12) ◽  
pp. 3616-3621 ◽  
Author(s):  
JA Hamilton ◽  
GA Whitty ◽  
H Stanton ◽  
J Wojta ◽  
M Gallichio ◽  
...  
Keyword(s):  
Plasminogen Activator ◽  
Human Monocyte ◽  
Mrna Levels ◽  
Human Monocytes ◽  
Colony Stimulating Factor ◽  
Gm Csf ◽  
Macrophage Colony Stimulating Factor ◽  
Macrophage Colony ◽  
Stimulating Factor ◽  
Pai 1

Macrophage colony-stimulating factor (M-CSF or CSF-1) and granulocyte- macrophage CSF (GM-CSF) have been shown to increase human monocyte urokinase-type plasminogen-activator (u-PA) activity with possible consequences for cell migration and tissue remodeling; because monocyte u-PA activity is likely to be controlled in part also by the PA inhibitors (PAIs) made by the cell, the effect of M-CSF and GM-CSF on human monocyte PAI-2 and PAI-1 synthesis was investigated. To this end, elutriation-purified human monocytes were treated in vitro with purified recombinant human M-CSF and GM-CSF, and PAI-2 and PAI-1 antigen and mRNA levels measured by specific enzyme-linked immunosorbent assays and Northern blot, respectively. Each CSF could enhance the protein and mRNA levels of PAI-2 and PAI-1 at similar concentrations for each product. This similar regulation of monocyte PAI expression in response to the CSFs contrasted with that found for the effects of lipopolysaccharide, transforming growth factor-beta and a glucocorticoid. Therefore, PAIs may be modulating the effects of the CSFs on monocyte u-PA activity at sites of inflammation and tissue remodeling.

scholarly journals Candida albicans Yeast and Germ Tube Forms Interfere Differently with Human Monocyte Differentiation into Dendritic Cells: a Novel Dimorphism-Dependent Mechanism To Escape the Host's Immune Response

2004 ◽  
Vol 72 (2) ◽  
pp. 833-843 ◽  
Author(s):  
Antonella Torosantucci ◽  
Giulia Romagnoli ◽  
Paola Chiani ◽  
Annarita Stringaro ◽  
Pasqualina Crateri ◽  
...  
Keyword(s):  
Dendritic Cells ◽  
Candida Albicans ◽  
Germ Tube ◽  
Immune Surveillance ◽  
Human Monocyte ◽  
Interleukin 4 ◽  
Human Monocytes ◽  
Necrosis Factor Alpha ◽  
Tnf Α ◽  
Mrna Transcripts

ABSTRACT The ability of Candida albicans to convert from the yeast (Y) form to mycelial forms through germ tube (GT) formation is considered a key feature of the transition of the organism from commensalism to virulence. We show here that human monocytes cultured with granulocyte-macrophage colony-stimulating factor and interleukin-4 (IL-4) after phagocytosis of Y forms did not differentiate into dendritic cells (DCs); they retained CD14, did not acquire CD1a, and were unable to express the maturation markers CD83 and CCR7. Moreover, they did not produce IL-12p70 but secreted IL-10. In addition, they spontaneously expressed high levels of tumor necrosis factor alpha (TNF-α), IL-6, and IL-8 mRNA transcripts and were able to induce proliferation of alloreactive memory but not naïve T lymphocytes. Conversely, monocytes that had phagocytosed GT forms differentiated into mature CD83+ and CCR7+ DCs; however, there was no up-regulation of CD40, CD80, and major histocompatibility complex class II, irrespective of lipopolysaccharide (LPS) treatment. In addition, these cells were unable to produce IL-12 even after LPS stimulation, but they were not functionally exhausted, as shown by their capacity to express TNF-α and IL-8 mRNA transcripts. These cells were able to prime naïve T cells but not to induce their functional polarization into effector cells. These data indicate that phagocytosis of Y and GT forms has profound and distinct effects on the differentiation pathway of monocytes. Thus, the differentiation of human monocytes into DCs appears to be tunable and exploitable by C. albicans to elude immune surveillance.

scholarly journals Human Bone Marrow-Derived Mesenchymal Stromal Cells Differentially Inhibit Cytokine Production by Peripheral Blood Monocytes Subpopulations and Myeloid Dendritic Cells

2015 ◽  
Vol 2015 ◽  
pp. 1-15 ◽  
Author(s):  
Paula Laranjeira ◽  
Joana Gomes ◽  
Susana Pedreiro ◽  
Monia Pedrosa ◽  
Antonio Martinho ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Dendritic Cells ◽  
Protein Expression ◽  
Peripheral Blood ◽  
Immune Cell ◽  
Human Bone ◽  
Human Bone Marrow ◽  
Mrna Levels ◽  
Myeloid Dendritic Cells ◽  
Experimental Conditions

The immunosuppressive properties of mesenchymal stromal/stem cells (MSC) rendered them an attractive therapeutic approach for immune disorders and an increasing body of evidence demonstrated their clinical value. However, the influence of MSC on the function of specific immune cell populations, namely, monocyte subpopulations, is not well elucidated. Here, we investigated the influence of human bone marrow MSC on the cytokine and chemokine expression by peripheral blood classical, intermediate and nonclassical monocytes, and myeloid dendritic cells (mDC), stimulated with lipopolysaccharide plus interferon (IFN)γ. We found that MSC effectively inhibit tumor necrosis factor- (TNF-)αand macrophage inflammatory protein- (MIP-) 1βprotein expression in monocytes and mDC, without suppressing CCR7 and CD83 protein expression. Interestingly, mDC exhibited the highest degree of inhibition, for both TNF-αand MIP-1β, whereas the reduction of TNF-αexpression was less marked for nonclassical monocytes. Similarly, MSC decreased mRNA levels of interleukin- (IL-) 1βand IL-6 in classical monocytes, CCL3, CCL5, CXCL9, and CXCL10 in classical and nonclassical monocytes, and IL-1βand CXCL10 in mDC. MSC do not impair the expression of maturation markers in monocytes and mDC under our experimental conditions; nevertheless, they hamper the proinflammatory function of monocytes and mDC, which may impede the development of inflammatory immune responses.

scholarly journals Lipoxin A4 and B4 are potent stimuli for human monocyte migration and adhesion: selective inactivation by dehydrogenation and reduction.

1996 ◽  
Vol 183 (1) ◽  
pp. 137-146 ◽  
Author(s):  
J F Maddox ◽  
C N Serhan
Keyword(s):  
Rank Order ◽  
Vascular Diseases ◽  
Human Monocyte ◽  
Oxidation Products ◽  
The Novel ◽  
Human Monocytes ◽  
Lipoxin A4 ◽  
Western Blots ◽  
Monocyte Migration ◽  
Monocyte Adherence

Monocyte recruitment and adherence are important events in inflammatory and vascular diseases. Here, we evaluated the actions of lipoxin A4 (LXA4) and LXB4, a series of lipoxygenase products from arachidonic acid generated by cell-cell interactions, on human monocytes. LXA4 and LXB4 (10(-7) M) each increased monocyte migration in chamber chemotaxis assays and, in migration under agarose, exhibited chemotactic indices similar to those of the chemotactic peptide formyl-methionyl-leucyl-phenylalanine at 10(-10)-10(-8) M and to the chemokine macrophage inflammatory protein-1 alpha (MIP-1 alpha) at 10(-8)-10(-7) M with a rank order of potency: Monocyte chemotactic protein-1 alpha > LXA4 approximately LXB4 approximately MIP-1 alpha. Lipoxins also stimulated monocyte adherence to laminin. In addition, human monocytes rapidly transformed LXA4 and LXB4 to several metabolites. LXB4 (> 80%) was converted within 30 s to new products, in a trend similar to that of LXA4. The novel monocyte-derived LXB4 products were identified as 5-oxo-6,7-dihydro-LXB4 and 6,7-dihydro-LXB4, indicating a role for site-selective dehydrogenation and reduction. Unlike monocytes, intact polymorphonuclear leukocytes (PMN) did not metabolize LXA4 in significant quantities, and only approximately 12% of exogenous LXB4 was omega-oxidized to 20-OH-LXB4 and 20-COOH-LXB4 by PMN. To determine if lipoxin conversion altered bioactivity, we evaluated the actions of these metabolites on monocytes. Each of the novel products of LXA4 and LXB4 from monocytes, namely oxo- and dihydrolipoxins, were essentially inactive in stimulating monocyte adherence. In contrast, the omega-oxidation products of LXB4 isolated from PMN were equipotent with LXB4 for monocyte adherence. Dehydrogenation of LXA4 in monocytes appears to be carried out by a 15-hydroxyprostaglandin dehydrogenase, which is present in human monocytes as determined by reverse transcription PCR and Western blots. Together, these results provide the first evidence that LXA4 and LXB4 are both potent stimulants for migration and adherence of human monocytes. Moreover, they underscore the importance of the major route of lipoxin metabolism in leukocytes, namely, the rapid dehydrogenation and inactivation carried out by monocytes.

scholarly journals Monocytes and macrophages synthesize and secrete thrombospondin

Blood ◽  
1985 ◽  
Vol 65 (1) ◽  
pp. 79-84 ◽  
Author(s):  
EA Jaffe ◽  
JT Ruggiero ◽  
DJ Falcone
Keyword(s):  
Culture Medium ◽  
Protein A ◽  
Sodium Dodecyl ◽  
Human Monocyte ◽  
Peritoneal Macrophages ◽  
Time Dependent ◽  
Enzyme Linked Immunosorbent Assay ◽  
Dependent Manner ◽  
Human Monocytes ◽  
Monocytes And Macrophages

hrombospondin, one of the major glycoproteins released from alpha- granules of thrombin-stimulated platelets, is a disulfide-linked trimer of 160,000-dalton subunits. Cultured human monocytes secreted thrombospondin (determined by an enzyme-linked immunosorbent assay) into the culture medium in a time-dependent manner (1.45 micrograms/10(6) cells/24 hr); secretion was totally blocked by cycloheximide (1 microgram/mL). 35S-thrombospondin was isolated from 35S-methionine-labeled human monocyte postculture medium with rabbit polyclonal anti-thrombospondin coupled to protein A-Sepharose. The immunoisolated 35S-thrombospondin migrated in sodium dodecyl sulfate- polyacrylamide gels after reduction with a molecular weight of 159,000. Similar results were obtained using mouse resident peritoneal macrophages. Elicited peritoneal macrophages harvested from mice pretreated with endotoxin, casein, or thioglycollate secreted much less thrombospondin than did resident macrophages harvested from control mice. Thus, monocytes and macrophages from two different species synthesize and secrete thrombospondin, and the rate of synthesis of thrombospondin appears to depend on the state of activation of the cells.

scholarly journals Distinct Gene Expression Profiling after Infection of Immature Human Monocyte-Derived Dendritic Cells by the Attenuated Poxvirus Vectors MVA and NYVAC

2007 ◽  
Vol 81 (16) ◽  
pp. 8707-8721 ◽  
Author(s):  
Susana Guerra ◽  
José Luis Nájera ◽  
José Manuel González ◽  
Luis A. López-Fernández ◽  
Nuria Climent ◽  
...  
Keyword(s):  
Gene Expression ◽  
Dendritic Cells ◽  
Gene Expression Profiling ◽  
Expression Profiling ◽  
Expression Profiles ◽  
Expression Patterns ◽  
Human Monocyte ◽  
Type I ◽  
Mrna Levels ◽  
Antigen Uptake

ABSTRACT Although recombinants based on the attenuated poxvirus vectors MVA and NYVAC are currently in clinical trials, the nature of the genes triggered by these vectors in antigen-presenting cells is poorly characterized. Using microarray technology and various analysis conditions, we compared specific changes in gene expression profiling following MVA and NYVAC infection of immature human monocyte-derived dendritic cells (MDDC). Microarray analysis was performed at 6 h postinfection, since these viruses induced extensive cytopathic effects, rRNA breakdown, and apoptosis at late times postinfection. MVA- and NYVAC-infected MDDC shared upregulation of 195 genes compared to uninfected cells: MVA specifically upregulated 359 genes, and NYVAC upregulated 165 genes. Microarray comparison of NYVAC and MVA infection revealed 544 genes with distinct expression patterns after poxvirus infection and 283 genes specifically upregulated after MVA infection. Both vectors upregulated genes for cytokines, cytokine receptors, chemokines, chemokine receptors, and molecules involved in antigen uptake and processing, including major histocompatibility complex genes. mRNA levels for interleukin 12β (IL-12β), beta interferon, and tumor necrosis factor alpha were higher after MVA infection than after NYVAC infection. The expression profiles of transcription factors such as NF-κB/Rel and STAT were regulated similarly by both viruses; in contrast, OASL, MDA5, and IRIG-I expression increased only during MVA infection. Type I interferon, IL-6, and Toll-like receptor pathways were specifically induced after MVA infection. Following MVA or NYVAC infection in MDDC, we found similarities as well as differences between these virus strains in the expression of cellular genes with immunological function, which should have an impact when these vectors are used as recombinant vaccines.

scholarly journals HLA-J, a Non-Pseudogene as a New Prognostic Marker for Therapy Response and Survival in Breast Cancer

2020 ◽  
Vol 80 (11) ◽  
pp. 1123-1133
Author(s):  
Franziska M. Würfel ◽  
Ralph M. Wirtz ◽  
Christoph Winterhalter ◽  
Mario Taffurelli ◽  
Donatella Santini ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Mrna Expression ◽  
Immune Cell ◽  
Therapy Response ◽  
Human Leukocyte ◽  
Progression Free Survival ◽  
Predictive Marker ◽  
Surface Proteins ◽  
Mrna Levels ◽  
Luminal B

AbstractThe human leukocyte antigen (HLA) genes are cell-surface proteins, essential for immune cell interaction. HLA-G is known for their high immunosuppressive effect and its potential as predictive marker in breast cancer. However, nothing is known about the HLA-J and its immunosuppressive, prognostic and predictive features, as it is assumed to be a “pseudogene” by in silico sequence interpretation. HLA-J, ESR1, ERBB2, KRT5 and KRT20 mRNA expression were analysed in 29 fresh frozen breast cancer biopsies and their corresponding resectates obtained from patients treated with neoadjuvant chemotherapy (NACT). mRNA was analysed with gene specific TaqMan-based Primer/Probe sets and normalized to Calmodulin 2. All breast cancer samples did express HLA-J and frequently increased HLA-J mRNA levels after NACT. HLA-J mRNA was significantly associated with overexpression of the ESR1 mRNA status (Spearman ρ 0,5679; p = 0.0090) and KRT5 mRNA (Spearman ρ 0,6121; p = 0.0041) in breast cancer core biopsies and dominated in luminal B subtype. Kaplan Meier analysis revealed that an increase of HLA-J mRNA expression after NACT had worse progression free survival (p = 0,0096), indicating a counterreaction of tumor tissues presumably to prevent elimination by enhanced immune infiltration induced by NACT. This counterreaction is associated with worse prognosis. To our knowledge this is the first study identifying HLA-J as a new predictive marker in breast cancer being involved in immune evasion mechanisms.

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