Analysis of hypoxia-associated dendritic cells in colitic mice and effects of probiotics on IL-10 production in inflammatory dendritic-cells under hypoxia

2019 ◽  
Vol 10 (7) ◽  
pp. 801-810
Author(s):  
T. Ogita ◽  
J. Miyamoto ◽  
Y. Hirabayashi ◽  
M. Rossi ◽  
G. Mazzarella ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Dendritic Cells ◽  
Hypoxia Inducible Factor ◽  
Flow Cytometric Analysis ◽  
Bifidobacterium Bifidum ◽  
Sodium Sulphate ◽  
Mesenteric Lymph Nodes ◽  
Cellular Mechanisms ◽  
Hypoxic Conditions ◽  
Anti Inflammatory

The aim of this study was to analyse hypoxia-associated dendritic cells (DCs) in colitic mice and the effects of probiotics on interleukin (IL)-10 production in inflammatory DCs under hypoxic conditions. Extensive hypoxia was observed in the colonic mucosa of dextran sodium sulphate-induced colitic mice. Flow cytometric analysis demonstrated that hypoxia-inducible factor-1α+ DCs in colonic lamina propria (CLP) lymphocytes and mesenteric lymph nodes (MLN) were more abundant in colitic mice than those in controls. Among three subsets of DCs, i.e. plasmacytoid DCs, conventional DCs (cDCs), and monocyte-derived DCs (mDCs), cDCs and mDCs were more abundant in CLP of colitic mice. Bone marrow-derived Flt-3L-induced DCs (Flt-DCs) but not bone marrow-derived GM-CSF-induced DCs (GM-DCs), incubated with 1% O2 exhibited an inflammatory phenotype, with higher CD86, IL-6, and tumour necrosis factor-α expression, and lower IL-10 levels than those in Flt-DCs incubated with 21% O2. The hypoxia-induced decrease in IL-10 expression in Flt-DCs was restored by Bifidobacterium bifidum JCM 1255T promoted IL-10 expression through the p38 pathway under normoxic conditions. The anti-inflammatory effects of B. bifidum JCM 1255T in Flt-DCs were mediated through different cellular mechanisms under hypoxic and normoxic conditions. B. bifidum JCM 1255T could be used therapeutically for its anti-inflammatory effects.

scholarly journals Bioactive Compounds from Polygala tenuifolia and Their Inhibitory Effects on Lipopolysaccharide-Stimulated Pro-inflammatory Cytokine Production in Bone Marrow-Derived Dendritic Cells

Plants ◽  
2020 ◽  
Vol 9 (9) ◽  
pp. 1240
Author(s):  
Le Ba Vinh ◽  
Myungsook Heo ◽  
Nguyen Viet Phong ◽  
Irshad Ali ◽  
Young Sang Koh ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Dendritic Cells ◽  
Inflammatory Cytokines ◽  
2D Nmr ◽  
Inhibitory Effects ◽  
Triterpenoid Saponins ◽  
Traditional Chinese Herbal Medicine ◽  
Polygala Tenuifolia ◽  
Anti Inflammatory ◽  
Pro Inflammatory Cytokines

The roots of Polygala tenuifolia Wild (Polygalaceae), which is among the most important components of traditional Chinese herbal medicine, have been widely used for over 1000 years to treat a variety of diseases. In the current investigation of secondary metabolites with anti-inflammatory properties from Korean medicinal plants, a phytochemical constituent study led to the isolation of 15 compounds (1–15) from the roots of P. tenuifolia via a combination of chromatographic methods. Their structures were determined by means of spectroscopic data such as nuclear magnetic resonance (NMR), 1D- and 2D-NMR, and liquid chromatography-mass spectrometry (LC-MS). As the obtained results, the isolated compounds were divided into two groups—phenolic glycosides (1–9) and triterpenoid saponins (10–15). The anti-inflammatory effects of crude extracts, fractions, and isolated compounds were investigated on the production of the pro-inflammatory cytokines interleukin (IL)-12 p40, IL-6, and tumour necrosis factor-α in lipopolysaccharide-stimulated bone marrow-derived dendritic cells. The IC50 values, ranging from 0.08 ± 0.01 to 21.05 ± 0.40 μM, indicated potent inhibitory effects of the isolated compounds on the production of all three pro-inflammatory cytokines. In particular, compounds 3–12, 14, and 15 showed promising anti-inflammatory activity. These results suggest that phenolic and triterpenoid saponins from P. tenuifolia may be excellent anti-inflammatory agents.

Anti-inflammatory Activity ofCarpinus tschonoskiiLeaves Extract in R848-stimulated Bone Marrow-derived Macrophages and Dendritic Cells

2012 ◽  
Vol 42 (1) ◽  
pp. 77 ◽  
Author(s):  
Sung-Ha Kang ◽  
Jung-Eun Koo ◽  
Hye-Jin Hong ◽  
Vivek Bhakta Mathema ◽  
Young-Sang Koh
Keyword(s):  
Bone Marrow ◽  
Dendritic Cells ◽  
Inflammatory Activity ◽  
Anti Inflammatory

scholarly journals The Anti-Inflammatory Properties of Citrus wilsonii Tanaka Extract in LPS-Induced RAW 264.7 and Primary Mouse Bone Marrow-Derived Dendritic Cells

Molecules ◽  
2017 ◽  
Vol 22 (7) ◽  
pp. 1213 ◽  
Author(s):  
Liping Cheng ◽  
Yujie Ren ◽  
Dingbo Lin ◽  
Shu’ang Peng ◽  
Bo Zhong ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Dendritic Cells ◽  
Mouse Bone Marrow ◽  
Raw 264.7 ◽  
Primary Mouse ◽  
Anti Inflammatory

Role of the Hypoxic Bone Marrow Microenvironment in Multiple Myeloma Tumor Progression.

Blood ◽  
2004 ◽  
Vol 104 (11) ◽  
pp. 2348-2348
Author(s):  
Kewal Asosingh ◽  
Hendrik De Raeve ◽  
Mark de Ridder ◽  
Guy A. Storme ◽  
Angelo Willems ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Bone Marrow ◽  
Mouse Model ◽  
Tumor Progression ◽  
Flow Cytometric Analysis ◽  
Surrogate Marker ◽  
Hypoxic Conditions ◽  
Flow Cytometric

Abstract Recently we reported that pre-clinical myeloma disease progression in the 5T2MM mouse model is characterized by predominant CD45+ MM-cells in the early, pre-angiogenic stage stage of slow tumor progression, followed by expansion of CD45− MM-cells during the subsequent angiogenic stage of progressive tumor growth. Unlike other cancer cells, multiple myeloma (MM) cells have to survive and to grow in a microenvironment which is already hypoxic by nature. This hypoxic bone marrow (BM) microenvironment is essential for normal hematopoiesis. However, the role of BM hypoxia in myeloma tumor progression is not known. Herein we addressed this topic in the 5T2MM mouse model. Flow cytometric analysis of control mice and 5T2MM diseased mice injected with pimonidazole hypoxyprobe indicated that both normal BM and myeloma infiltrated BM are hypoxic. However, in myelomatous BM the hypoxia was significantly decreased. Analysis of HIF-1a expression, a surrogate marker of hypoxia, by flow cytometry also demonstrated significantly lower levels of hypoxia in myeloma infiltrated BM. HIF-1a expression was found in 5T2MM-cells and was significantly higher compared to the non-tumor cell fraction. In vitro culturing of 5T2MM cells under hypoxic conditions, indicated increased activation of apoptosis inducing caspase-3 in the CD45− MM-fraction, but not in the CD45+ 5T2MM-cells, suggesting that native BM hypoxia selects the tumor population for tumor initiating CD45+ 5T2MM-cells. Although angiogeneic switch and angiogeneic heterogeneity has been reported in MM, the role of myeloma associated angiogensis is remains unclear. The decreased hypoxia in myeloma infiltrated BM adds strength to the hypothesis that myeloma associated neovascularization is functional by increasing BM oxygenation. The data also suggest that the angiogenesis allows expansion of CD45− 5T2MM-cells by decreasing BM hypoxia. All together, these findings suggest an important role of BM hypoxia in myeloma tumor progression.

Hypoxia Induces Imatinib Resistance in CML Cell Lines.

Blood ◽  
2006 ◽  
Vol 108 (11) ◽  
pp. 4387-4387
Author(s):  
Daniela Buglio ◽  
Piera La Cava ◽  
Fabio Stagno ◽  
Annalisa Chiarenza ◽  
Salvatore Berretta ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Cell Lines ◽  
Kinase Inhibitor ◽  
Critical Role ◽  
Hypoxia Inducible Factor ◽  
Leukemic Cell ◽  
Reversible Inhibitor ◽  
Imatinib Resistance ◽  
Downstream Target ◽  
Hypoxic Conditions

Abstract Background: Imatinib is a potent tyrosine kinase inhibitor that is highly effective in the treatment of chronic myeloid leukemia. However, some patients are resistant to imatinib. Some of the mechanisms leading to imatinib resistance include amplification of the BCR-ABL gene, determining overexpression of the protein, and mutations in the BCR-ABL protein with alteration of imatinib binding sites. Imatinib uptake is an active process mediated by a group of transporters that includes the organic cation transporters (hOCT) and it has been shown that different expression of OCT1 may play a critical role on intracellular drug levels and, hence, resistance to imatinib. Hypoxia is another important factor that may contribute to drug resistance. Hypoxia-Inducible Factor (HIF-1α) and its downstream target, Vascular endothelial Growth Factor (VEGF), have been shown to be overexpressed in leukemic bone marrow specimens compared to normal bone marrow. The purpose of this study is to determine if the hypoxic conditions and OCT1 inhibition affect imatinib sensitivity. Methods: Chronic myeloid leukemic cell line K562 and LAMA84 were cultured in 10% serum RPMI medium under hypoxic (3% O2) or normoxic (21% O2) conditions. All samples were treated with imatinib 1μM ± prazosin 13 μM (OCT1 reversible inhibitor) for 24 hs. Results: Cells treated with imatinib and cultured under hypoxic conditions demonstrated decreased apoptosis and increased cell viability compared to normoxic conditions (K562 Annexin + cells 62% vs 94%, p= 0.003, LAMA84 Annexin + cells 61% vs 92%, p=0.0028). The addition of prazosin almost abrogated imatinib efficacy in normoxic environment but did not modify the effect of imatinib under hypoxic conditions. Conclusions: Our data confirm that OCT1 is the most important imatinib carrier. Exposure of CML cell lines to an hypoxic environment results in reduced sensitivity to imatinib and this effect wasn’t affected by OCT1 inhibition. Search for underlying mechanisms of these findings are in progress.

scholarly journals Inhibitory Effects of Cucurbitane-Type Triterpenoids from Momordica charantia Fruit on Lipopolysaccharide-Stimulated Pro-Inflammatory Cytokine Production in Bone Marrow-Derived Dendritic Cells

Molecules ◽  
2021 ◽  
Vol 26 (15) ◽  
pp. 4444
Author(s):  
Thao Quyen Cao ◽  
Nguyen Viet Phong ◽  
Jang Hoon Kim ◽  
Dan Gao ◽  
Hoang Le Tuan Anh ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Dendritic Cells ◽  
Inflammatory Cytokine ◽  
Cytokine Production ◽  
Momordica Charantia ◽  
Ionization Mass ◽  
Inflammatory Cytokine Production ◽  
Chemical Structures ◽  
Tnf Α ◽  
Anti Inflammatory

The bitter melon, Momordica charantia L., was once an important food and medicinal herb. Various studies have focused on the potential treatment of stomach disease with M. charantia and on its anti-diabetic properties. However, very little is known about the specific compounds responsible for its anti-inflammatory activities. In addition, the in vitro inhibitory effect of M. charantia on pro-inflammatory cytokine production by lipopolysaccharide (LPS)-stimulated bone marrow-derived dendritic cells (BMDCs) has not been reported. Phytochemical investigation of M. charantia fruit led to the isolation of 15 compounds (1−15). Their chemical structures were elucidated spectroscopically (one- and two-dimensional nuclear magnetic resonance) and with electrospray ionization mass spectrometry. The anti-inflammatory effects of the isolated compounds were evaluated by measuring the production of the pro-inflammatory cytokines interleukin IL-6, IL-12 p40, and tumor necrosis factor α (TNF-α) in LPS-stimulated BMDCs. The cucurbitanes were potent inhibitors of the cytokines TNF-α, IL-6, and IL-12 p40, indicating promising anti-inflammatory effects. Based on these studies and in silico simulations, we determined that the ligand likely docked in the receptors. These results suggest that cucurbitanes from M. charantia are potential candidates for treating inflammatory diseases.

scholarly journals Lipopolysaccharide-Activated Bone Marrow-Derived Dendritic Cells Suppress Allergic Airway Inflammation by Ameliorating the Immune Microenvironment

2021 ◽  
Vol 12 ◽  
Author(s):  
Zhihui Min ◽  
Yuzhen Zeng ◽  
Tao Zhu ◽  
Bo Cui ◽  
Ruolin Mao ◽  
...  
Keyword(s):  
Bone Marrow ◽  
T Cells ◽  
Dendritic Cells ◽  
Airway Inflammation ◽  
Inflammatory Cytokines ◽  
Phosphorylation Level ◽  
Th2 Immune Response ◽  
Anti Inflammatory

BackgroundPrevious studies have shown that lipopolysaccharide (LPS)-activated bone marrow-derived dendritic cells (DClps) might induce tolerance in autoimmune and cancer models in vivo, whereas it remains unclear whether DClps could play a role in allergic disease model. Herein, we aimed to elucidate the potential effects of DClps on OVA-sensitized/challenged airway inflammation in a mouse model, which may help facilitate the application of specific tolerogenic dendritic cells (tolDC) in allergic asthma in the future.MethodsThe phenotype and function of immature DC (DCia), DClps or IL-10-activated-DC (DC10) were determined. OVA-sensitized/challenged mice were treated with OVA-pulsed DCia or DClps or DC10. We assessed the changes of histopathology, serum total IgE level, pulmonary signal transducers and activators of transcription (STAT), pulmonary regulatory T cells (Tregs), and airway recall responses to OVA rechallenge, including proliferation and cytokine secretory function of pulmonary memory CD4+ T cells in the treated mice.ResultsDClps exhibited low levels of CD80 and MHCII and increased levels of anti-inflammatory cytokines such as IL-10 and TGF-β. Additionally, DClps treatment dramatically diminished infiltration of inflammatory cells, eosinophilia, serum IgE and STAT6 phosphorylation level, increased the number of pulmonary Tregs. In addition, DClps treatment decreased the proliferation of pulmonary memory CD4+ T cells, which further rendered the downregulation of Th2 cytokines in vitro.ConclusionLPS stimulation may lead to a tolerogenic phenotype on DC, and thereby alleviated the Th2 immune response of asthmatic mice, possibly by secreting anti-inflammatory cytokines, inhibiting pulmonary memory CD4+ T cells, downregulating pulmonary STAT6 phosphorylation level and increasing pulmonary Tregs.

Sign in / Sign up

Export Citation Format

Share Document