scholarly journals Cannabinoid type 2 receptor (CB2R) distribution in dermatomyositis skin and peripheral blood mononuclear cells (PBMCs) and in vivo effects of LenabasumTM

2022 ◽  
Vol 24 (1) ◽  
Author(s):  
Spandana Maddukuri ◽  
Jay Patel ◽  
De Anna Diaz ◽  
Kristen L. Chen ◽  
Maria Wysocka ◽  
...  
Keyword(s):  
Dendritic Cells ◽  
Mononuclear Cells ◽  
Cytokine Production ◽  
Immune Cell ◽  
Cell Populations ◽  
Peripheral Blood Mononuclear ◽  
Blood Mononuclear Cells ◽  
Ifn Γ

Abstract Background Lenabasum is a cannabinoid type 2 receptor (CB2R) reverse agonist that demonstrates anti-inflammatory effects in vivo and in vitro in dermatomyositis (DM) and is currently being investigated for therapeutic potential. The purpose of our study is to investigate CB2R distribution as well as the effects of lenabasum in DM. Methods Immunohistochemistry staining (IHC) was utilized to examine immune cell and cytokine production changes in lesional DM skin biopsies from lenabasum and placebo-treated patients. CB2R expression in various immune cell populations within DM skin was investigated with image mass cytometry (IMC), whereas flow cytometry elucidated CB2R expression in DM peripheral blood mononuclear cells (PBMCs) as well as cytokine production by CB2R-expressing cell populations. Results After 12 weeks of lenabasum treatment, IHC staining showed that CD4+ T cells, CB2R, IL-31, IFN-γ, and IFN-β cytokines were downregulated. IFN-γ and IFN-β mRNA decreased in lesional DM skin but not in PBMCs. IMC findings revealed that CB2R was upregulated in DM lesional skin compared to HC skin and DM PBMCs (p<0.05). In DM skin, CB2R was upregulated on dendritic cells, B cells, T cells, and macrophages while dendritic cells had the greatest expression in both DM skin and PBMCs (p<0.05). These CB2R+ cells in the skin produce IL-31, IL-4, IFN-γ, and IFN-β. Conclusion Our findings of differential CB2R expression based on location and cell type suggest modes by which lenabasum may exert anti-inflammatory effects in DM and highlights dendritic cells as potential therapeutic targets.

Renal Cell Carcinoma Induces Prostaglandin E2 and T-Helper Type 2 Cytokine Production in Peripheral Blood Mononuclear Cells

2003 ◽  
Vol 10 (4) ◽  
pp. 455-462 ◽  
Author(s):  
Gordon P. Smyth ◽  
Philip P. Stapleton ◽  
Catherine B. Barden ◽  
Juan R. Mestre ◽  
Tracy A. Freeman ◽  
...  
Keyword(s):  
Renal Cell Carcinoma ◽  
Peripheral Blood Mononuclear Cells ◽  
Renal Cell ◽  
Mononuclear Cells ◽  
Cytokine Production ◽  
T Helper ◽  
Peripheral Blood Mononuclear ◽  
Blood Mononuclear Cells ◽  
Helper Type

Neopterin suppresses the activity of tryptophan-degrading enzyme indoleamine 2,3-dioxygenase in human peripheral blood mononuclear cells

Pteridines ◽  
2013 ◽  
Vol 24 (3) ◽  
pp. 237-243
Author(s):  
Sebastian Schroecksnadel ◽  
Elena-Sophia Ledjeff ◽  
Johanna Gostner ◽  
Christiana Winkler ◽  
Katharina Kurz ◽  
...  
Keyword(s):  
Peripheral Blood Mononuclear Cells ◽  
Peripheral Blood ◽  
Mononuclear Cells ◽  
Human Peripheral Blood ◽  
Peripheral Blood Mononuclear ◽  
Indoleamine 2,3 Dioxygenase ◽  
Blood Mononuclear Cells ◽  
Ifn Γ

AbstractIn vitro, large amounts of neopterin are released from human monocyte-derived macrophages and dendritic cells primarily upon stimulation with Th1-type cytokine interferon-γ (IFN-γ). IFN-γ also induces the enzyme indoleamine 2,3-dioxygenase (IDO), which degrades tryptophan (TRP) to form kynurenine (KYN). IDO-mediated TRP catabolism is very effective in suppressing the proliferation of T lymphocytes as well as of pathogens in vitro and in vivo. In this study, we investigated whether exogenously added neopterin may influence IDO activity in resting and in stimulated peripheral blood mononuclear cells (PBMC). PBMC were isolated from healthy donors, and neopterin was added in a concentration range from 0.01 to 50 μmol/L. After 30 min, PBMC were stimulated or not with 10 μg/mL of mitogen phytohemagglutinin (PHA). After 48 h, culture supernatants were collected, KYN and TRP concentrations were measured by high-performance liquid chromatography, and the ratio of KYN vs. TRP was calculated as an estimate of IDO activity. Spontaneous as well as PHA-induced TRP breakdown was suppressed by exogenously added neopterin in a dose-dependent way; the lowest active concentration of neopterin was <100 nmol/L. As neopterin concentrations in the nanomolar range are commonly observed in patients suffering from infections, sepsis, or uremia, our results suggest that neopterin formation might also serve as a feedback mechanism to slow down TRP degradation in vivo.

In vitro cytokine synthesis in unstimulated and mitogen-stimulated peripheral blood mononuclear cells from individuals with schizophrenia

2019 ◽  
Vol 67 (7) ◽  
pp. 1053-1060
Author(s):  
Elżbieta Kozłowska ◽  
Paulina Żelechowska ◽  
Adam Wysokiński ◽  
Paweł Rasmus ◽  
Anna Łucka ◽  
...  
Keyword(s):  
Immune System ◽  
Peripheral Blood Mononuclear Cells ◽  
Peripheral Blood ◽  
Mononuclear Cells ◽  
Immune Cell ◽  
Peripheral Blood Mononuclear ◽  
Spontaneous Production ◽  
Blood Mononuclear Cells ◽  
Ifn Γ

Increasing evidence has shown that the immune system is involved in the schizophrenia development, with alterations in immune cell reactivity being one possible factor contributing to its pathogenesis. The purpose of the study was to evaluate in vitro the capability of peripheral blood mononuclear cells (PBMCs) obtained from subjects with schizophrenia and controls to engage in spontaneous and phytohemagglutinin (PHA)-stimulated cytokine production. The concentrations of various cytokines (interleukin (IL)-1β, IL-17A, tumor necrosis factor (TNF), interferon (IFN)-γ and IL-10) in supernatants from cultured PBMCs were measured using the cytometric bead array. No significant differences in the spontaneous production of IL-1β, IL-17A, IFN-γ and IL-10 by PBMCs were detected between individuals with schizophrenia and controls. TNF synthesis by PBMCs was found to be lower among those with schizophrenia. In all subjects and controls, greater cytokine generation was associated with PBMCs treated with PHA compared with those that were not. The PBMCs from people with schizophrenia displayed considerably higher sensitivity to mitogen stimulation, as the production of IL-17A, TNF and IFN-γ was at least threefold of that observed in healthy subjects, which may be driven by antipsychotics taken by patients with schizophrenia. Correlation was observed between spontaneous production of IFN-γ and Positive and Negative Syndrome Scale G subscore (which measures the general symptoms of schizophrenia) and between PHA-stimulated synthesis of IL–17A and G subscore. Our data confirm that the immune system dysregulation may underlie schizophrenia pathophysiology. There is a potential possibility that immunological tests could be used as a diagnostic, therapeutic and side-effects biomarker for schizophrenia, but further studies are needed.

scholarly journals Impact of Sodium Butyrate Treatment in LPS-Stimulated Peripheral Blood Mononuclear Cells of Poorly Controlled Type 2 DM

2021 ◽  
Vol 12 ◽  
Author(s):  
Heri Wibowo ◽  
Dante S. Harbuwono ◽  
Dicky L. Tahapary ◽  
Rona Kartika ◽  
Saraswati Pradipta ◽  
...  
Keyword(s):  
Peripheral Blood Mononuclear Cells ◽  
Sodium Butyrate ◽  
Peripheral Blood ◽  
Mononuclear Cells ◽  
Peripheral Blood Mononuclear ◽  
Tnf Α ◽  
Blood Mononuclear Cells ◽  
Butyrate Treatment ◽  
Ifn Γ

Type 2 diabetes mellitus (T2DM) is associated with chronic low-grade inflammation, which is marked by the dysregulation of innate and adaptive immune responses. Therefore, reducing inflammation, possibly through an immunoregulatory agent, may play a role in T2DM treatment. Butyrate is the most potent short-chain fatty acid (SCFA), and it exerts anti-inflammatory properties by inhibiting histone deacetylase activity. As an immunoregulatory agent, sodium butyrate can inhibit nuclear factor kB (NF-kB) activation and reduce the production of pro-inflammatory cytokines in immune cells. The aim of the study was to measure the level of plasma butyrate in poorly controlled T2DM and normoglycemic participants and to compare the response of peripheral blood mononuclear cells (PBMCs) to sodium butyrate treatment between the groups by measuring production of the following cytokines: tumor necrosis factor (TNF)-α, interleukin (IL)-6, interferon (IFN)-γ, IL-13, and IL-10. The in vitro study examined the PBMCs of 15 participants with poorly controlled T2DM and 15 normoglycemic participants. PBMCs were cultured with the following stimulations for two days at a temperature of 37°C and 5% CO2: 100 ng/mL lipopolysaccharide (LPS), 1 mM sodium butyrate, or a combination of 100 ng/mL LPS and 1 mM sodium butyrate. Plasma butyrate was measured using gas chromatography-mass spectrometry, and cytokines from culture supernatant were analyzed using magnetic beads multiplex assay. Plasma butyrate levels in participants with poorly controlled T2DM did not significantly differ from those in normoglycemic participants (p = 0.105). Compared to treatment with an LPS-stimulated PBMC culture, treatment with 1 mM sodium butyrate reduced the levels of TNF-α (p &lt; 0.039) and IFN-γ (p &lt; 0.038) in normoglycemic participants. The same general trend was seen in PBMC from participants with poorly controlled T2DM, but higher variability appeared to preclude statistical significance. These data suggest that butyrate may modulate inflammatory cytokine production in human PBMCs, but more research is needed to determine if butyrate is anti-inflammatory in poorly controlled T2DM.

scholarly journals Functional dendritic cells are required for transfusion-induced sensitization in canine marrow graft recipients

Blood ◽  
1988 ◽  
Vol 71 (4) ◽  
pp. 1138-1140 ◽  
Author(s):  
HJ Deeg ◽  
J Aprile ◽  
R Storb ◽  
TC Graham ◽  
R Hackman ◽  
...  
Keyword(s):  
Dendritic Cells ◽  
Mononuclear Cells ◽  
Uv Light ◽  
Marrow Graft ◽  
Peripheral Blood Mononuclear ◽  
Leukocyte Population ◽  
Accessory Function ◽  
Blood Mononuclear Cells ◽  
Total Body

Untransfused dogs given 9.2 Gy total-body irradiation and hematopoietic grafts from DLA-identical littermate donors uniformly achieve sustained engraftment, whereas dogs given three transfusions (Tx) of whole blood from the intended marrow donor 24, 17 and 10 days pretransplant uniformly reject their graft. Sensitization appears to be mediated by peripheral blood mononuclear cells and can be prevented by prior irradiation of the Tx product with UV light, known to inactivate leukocytes, in particular, cells with accessory function. In the present study we investigated which leukocyte population was responsible for Tx-induced sensitization and subsequent marrow graft rejection. Surprisingly, neither monocytes nor macrophages or dendritic cells induced sensitization, and all dogs so treated achieved engraftment; however, all four evaluable dogs transfused with UV- exposed blood to which small numbers of normal dendritic cells (12.5 x 10(3)/kg) were added rejected their marrow graft. Among five dogs given UV-exposed blood and normal monocytes (12.5 x 10(3)/kg) only one rejected its graft, and four achieved sustained engraftment. We conclude that donor dendritic cells are necessary, albeit not sufficient for in vivo sensitization. Sensitization is prevented by elimination or inactivation of dendritic cell.

scholarly journals Analysis of Swine Conventional Dendritic Cells, DEC205+CD172a+/−CADM1+, from Blood and Spleen in Response to PRRSV and PEDV

Viruses ◽  
2019 ◽  
Vol 11 (11) ◽  
pp. 1001 ◽  
Author(s):  
Héctor Parra-Sánchez ◽  
Lorena Bustamante-Córdova ◽  
Mónica Reséndiz ◽  
Verónica Mata-Haro ◽  
Araceli Pinelli-Saavedra ◽  
...  
Keyword(s):  
T Cells ◽  
Dendritic Cells ◽  
Mononuclear Cells ◽  
Cytokine Production ◽  
Respiratory Syndrome Virus ◽  
Peripheral Blood Mononuclear ◽  
Naive T Cells ◽  
Diarrhea Virus ◽  
Naïve T Cells ◽  
Ifn Γ

Conventional dendritic cells (cDCs) cannot be infected by porcine reproductive and respiratory syndrome virus (PRRSV) but respond to infection via cytokine production, indicating a possible role in initiation/regulation of the immune response against PRRSV. In this work, we evaluated the responses of splenic and blood cDCs, with DEC205+CADM1+CD172a+/− phenotype, as well as those of CD163+ cells against PRRSV and porcine epidemic diarrhea virus (PEDV). Both populations were incubated in the presence of PRRSV or PEDV with and without naïve CD3+ T cells, and cytokine responses were evaluated by qPCR and ELISA. Our results showed that cDCs, but not CD163+ cells, produced IL-12 in response to PRRSV. PEDV did not induce IL-12 production. Cocultures of cDCs and autologous naïve CD3+ cells resulted in decreased IL-12 production and low expression of IFN-γ transcripts in response to PRRSV. Interestingly, cDCs increased the proliferation of naïve T cells in the presence of PRRSV compared with that achieved with monocytes and peripheral blood mononuclear cells (PBMCs). Cocultures of CD163+ cells induced IL-10 and IL-4 expression in the presence of PRRSV and PEDV, respectively. In conclusion, cDCs can selectively produce IL-12 in response to PRRSV but poorly participate in the activation of naïve T cells.

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