scholarly journals CML derived exosomes promote tumor favorable functional performance in T cells

BMC Cancer ◽  
2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Nazli Jafarzadeh ◽  
Mohammad Ali Gholampour ◽  
Mohammad-Reza Alivand ◽  
Saeideh Kavousi ◽  
Laleh Arzi ◽  
...  
Keyword(s):  
Bone Marrow ◽  
T Cells ◽  
Cord Blood ◽  
Inflammatory Cytokines ◽  
Interleukin 6 ◽  
Interleukin 10 ◽  
Myelogenous Leukemia ◽  
No Production ◽  
Intracellular Ros ◽  
Anti Inflammatory

Abstract Background Leukemic cells facilitate the creation of the tumor-favorable microenvironment in the bone marrow niche using their secreted factors. There are not comprehensive details about immunosuppressive properties of chronic myelogenous leukemia-derived exosomes in the bone marrow stromal and immune compartment. We explained here that K562-derived exosomes could affect the gene expression, cytokine secretion, nitric oxide (NO) production, and redox potential of human primary cord blood-derived T cells (CB T cells). Methods Human primary cord blood-derived T cells were treated with K562-derived exosomes. We evaluated the expression variation of some critical genes activated in suppressor T cells. The alterations of some inflammatory and anti-inflammatory cytokines levels were assessed using ELISA assay and real-time PCR. Finally, NO production and intracellular ROS level in CB T cells were evaluated using Greiss assay and flow cytometry, respectively. Results Our results showed the over-expression of the genes involved in inhibitory T cells, including NQO1, PD1, and FoxP3. In contrast, genes involved in T cell activation such as CD3d and NFATc3 have been reduced significantly. Also, the expression of interleukin 10 (IL-10) and interleukin 6 (IL-6) mRNAs were significantly up-regulated in these cells upon exosome treatment. In addition, secretion of the interleukin 10, interleukin 6, and interleukin 17 (IL-17) proteins increased in T cells exposed to K562-derived exosomes. Finally, K562-derived exosomes induce significant changes in the NO production and intracellular ROS levels in CB T cells. Conclusions These results demonstrate that K562-derived exosomes stimulate the immunosuppressive properties in CB-derived T cells by inducing anti-inflammatory cytokines such as IL-10, reducting ROS levels, and arising of NO synthesis in these cells. Moreover, considering the elevation of FOXP3, IL-6, and IL-17 levels in these cells, exosomes secreted by CML cells may induce the fates of T cells toward tumor favorable T cells instead of conventional activated T cells.

Abstract 44: Interleukin-27 Signaling is a Critical Regulator of Inflammation in Atherosclerosis

2013 ◽  
Vol 33 (suppl_1) ◽  
Author(s):  
Ekaterina Koltsova ◽  
Gisen Kim ◽  
Sibylle von Vietinghoff ◽  
Mitchell Kronenberg ◽  
Klaus Ley
Keyword(s):  
Bone Marrow ◽  
T Cells ◽  
Inflammatory Cytokines ◽  
Arterial Wall ◽  
Antigen Presenting Cells ◽  
Cytokine Signaling ◽  
Interleukin 27 ◽  
Anti Inflammatory ◽  
Antigen Presenting

Atherosclerosis is chronic inflammatory disease, which affects blood vessels. While the pro-atherogenic role of various inflammatory cytokines was broadly investigated, less is known about contribution of anti-inflammatory cytokines with regard to their ability to control inflammation in vivo. Interleukin 27 (IL-27) was shown to play immunosuppressive function via multiple mechanisms. We tested whether IL-27 signaling is important to restrain inflammation in mouse models of atherosclerosis. We transplanted bone marrow from Il27ra -/- or Il27ra +/+ mice into atherosclerosis prone Ldlr -/- littermates. Recipients of Il27ra -/- marrow showed significantly larger atherosclerotic lesions in aortic roots, aortic arches and, most strikingly, in the abdominal aorta. Aortas contained more CD45 + leukocytes and CD4 + T cells, which produced pro-atherogenic cytokines IL-17A and TNF-α. Concomitantly, the levels of IL-17A and IL-6 were significantly elevated in aortic tissue. These cytokines normally suppressed by IL-27, regulated the expression of CCL2 and other chemokines, which in turn led to accumulation of myeloid CD11b + and CD11c + cells in aortas, atherosclerotic plaque growth and disease progression. Moreover, using our recently developed live imaging by two-photon microscopy, we found enhanced interaction between antigen presenting cells and T cells in the arterial wall of Il27ra deficient mice. Overall, IL-27 signaling in bone marrow-derived cells regulates atherosclerosis by controlling interaction of antigen presenting cells and T cells in the arterial wall and therefore curbing Th17 and Th1 lineage differentiation, TNF and IL-17 dependent chemokine expression and subsequent myeloid cell accumulation. Thus, our work establishes the importance of anti-inflammatory cytokine signaling in atherosclerosis and demonstrates novel anti-atherogenic role of IL-27.

scholarly journals Inflammatory Cytokines Response to Isometric Handgrip Exercise and the Effects of Duration and Intensity of the Isometric Effort in Prehypertensive Subjects

2022 ◽  
Author(s):  
GODSDAY UDOJI OGBUTOR ◽  
Eze Kingsley Nwangwa ◽  
Collins Ogbeivor ◽  
Nkemakonam Ezeonu ◽  
Ephraim Chukwuemeka ◽  
...  
Keyword(s):  
Chronic Diseases ◽  
Inflammatory Cytokines ◽  
Interleukin 6 ◽  
Interleukin 10 ◽  
Handgrip Exercise ◽  
Isometric Handgrip ◽  
Exercise Protocol ◽  
Isometric Effort ◽  
Isometric Handgrip Exercise ◽  
Anti Inflammatory

Abstract BACKGROUND Chronic low grade systemic inflammation has been identified as a major risk factor for chronic diseases. The potential for physical exercise to induce anti-inflammatory effect is now increasingly being explored but there is paucity of data regarding the effects isometric exercise on inflammatory cytokines. The objective of this study was to investigate the responses of selected inflammatory cytokines to isometric handgrip exercise and identify possible effects of intensity and duration of the isometric effort on these variables. CASE PRESENTATION: A total of one hundred and ninety two (N=192) sedentary pre-hypertensive subjects, aged between 30-50years were recruited into the study and randomly distributed into three groups of 64 subjects each. The subjects performed a 24 consecutive day’s isometric hand grip exercise at 30% Maximum Voluntary Contraction. At the end of the 24 days, the group one (GP1) discontinued with the exercise protocol while the group two (GP2) continued the exercise protocol for another 24 consecutive days and the group three (GP3) continued with the exercise protocol for another 24 consecutive days but at 50%MVC. The parameters used to assess for the inflammatory cytokine variables included interleukin 10, interleukin 6 and tumor necrotic factor. At the end of the study, there was an increase in the resting values of interleukin 10 across the three groups while the resting values of interleukin 6 and tumor necrotic factor reduced significantly across groups. CONCLUSIONS: The reductions noted in the pro-inflammatory cytokines and increase in the anti-inflammatory cytokines could have a positive impact in the management of chronic diseases. It was also found that increase in intensity and/or duration produced more proportionate effect.

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.

scholarly journals Immunomodulatory Effect of Chinese Herbal Medicine Formula Sheng-Fei-Yu-Chuan-Tang in Lipopolysaccharide-Induced Acute Lung Injury Mice

2013 ◽  
Vol 2013 ◽  
pp. 1-12 ◽  
Author(s):  
Chia-Hung Lin ◽  
Ching-Hua Yeh ◽  
Li-Jen Lin ◽  
Shulhn-Der Wang ◽  
Jen-Shu Wang ◽  
...  
Keyword(s):  
Nitric Oxide ◽  
Acute Lung Injury ◽  
Lung Injury ◽  
Inflammatory Cytokines ◽  
Interleukin 1 ◽  
Reactive Oxygen Species Generation ◽  
Interleukin 10 ◽  
Interleukin 4 ◽  
No Production ◽  
Anti Inflammatory

Traditional Chinese medicine formula Sheng-Fei-Yu-Chuan-Tang (SFYCT), consisting of 13 medicinal plants, was used to treat patients with lung diseases. This study investigated the immunoregulatory effect of SFYCT on intratracheal lipopolysaccharides- (LPS-) challenged acute lung injury (ALI) mice. SFYCT attenuated pulmonary edema, macrophages, and neutrophils infiltration in the airways. SFYCT decreased inflammatory cytokines, including tumor necrosis factor-α(TNFα), interleukin-1β, and interleukin-6 and inhibited nitric oxide (NO) production but increased anti-inflammatory cytokines, interleukin-4, and interleukin-10, in the bronchoalveolar lavage fluid of LPS-challenged mice. TNFαand monocyte chemotactic protein-1 mRNA expression in the lung of LPS-challenged mice as well as LPS-stimulated lung epithelial cell and macrophage were decreased by SFYCT treatment. SFYCT treatment also decreased the inducible nitric oxide synthase expression and phosphorylation of nuclear factor-κB (NF-κB) in the lung of mice and macrophage with LPS stimulation. SFYCT treatment dose dependently decreased the LPS-induced NO and reactive oxygen species generation in LPS-stimulated macrophage. In conclusion, SFYCT attenuated lung inflammation during LPS-induced ALI through decreasing inflammatory cytokines production while increasing anti-inflammatory cytokines production. The immunoregulatory effect of SFYCT is related to inhibiting NF-κB phosphorylation.

A comparison of murine T-cell–depleted adult bone marrow and full-term fetal blood cells in hematopoietic engraftment and immune reconstitution

Blood ◽  
2002 ◽  
Vol 99 (1) ◽  
pp. 364-371 ◽  
Author(s):  
Benny J. Chen ◽  
Xiuyu Cui ◽  
Gregory D. Sempowski ◽  
Maria E. Gooding ◽  
Congxiao Liu ◽  
...  
Keyword(s):  
Stem Cells ◽  
Bone Marrow ◽  
T Cells ◽  
T Cell ◽  
Cord Blood ◽  
Blood Cells ◽  
Immune Reconstitution ◽  
Full Term ◽  
Fetal Blood ◽  
Adult Bone

Umbilical cord blood has been increasingly used as a source of hematopoietic stem cells. A major area of concern for the use of cord blood transplantation is the delay in myeloid and lymphoid recovery. To directly compare myeloid and lymphoid recovery using an animal model of bone marrow and cord blood as sources of stem cells, hematopoietic engraftment and immune recovery were studied following infusion of T-cell–depleted adult bone marrow or full-term fetal blood cells, as a model of cord blood in a murine allogeneic transplantation model (C57BL/6 [H-2b] → BALB/c [H-2d]). Allogeneic full-term fetal blood has poorer radioprotective capacity but greater long-term engraftment potential on a cell-to-cell basis compared with T-cell–depleted bone marrow. Allogeneic full-term fetal blood recipients had decreased absolute numbers of T, B, and dendritic cells compared with bone marrow recipients. Splenic T cells in allogeneic full-term fetal blood recipients proliferated poorly, were unable to generate cytotoxic effectors against third-party alloantigens in vitro, and failed to generate alloantigen-specific cytotoxic antibodies in vivo. In addition, reconstituting T cells in fetal blood recipients had decreased mouse T-cell receptorδ single-joint excision circles compared with bone marrow recipients. At a per-cell level, B cells from fetal blood recipients did not proliferate as well as those found in bone marrow recipients. These results suggest that full-term fetal blood can engraft allogeneic hosts across the major histocompatibility barrier with slower hematopoietic engraftment and impaired immune reconstitution.

scholarly journals Regulation of the Anti-Inflammatory Cytokines Interleukin-4 and Interleukin-10 during Pregnancy

2014 ◽  
Vol 5 ◽  
Author(s):  
Piyali Chatterjee ◽  
Valorie L. Chiasson ◽  
Kelsey R. Bounds ◽  
Brett M. Mitchell
Keyword(s):  
Inflammatory Cytokines ◽  
Interleukin 10 ◽  
Interleukin 4 ◽  
Anti Inflammatory

Transcription of AML1/ETO in bone marrow and cord blood of individuals without acute myelogenous leukemia

Blood ◽  
2002 ◽  
Vol 100 (6) ◽  
pp. 2267-2267 ◽  
Author(s):  
Jorg Basecke ◽  
Lukas Cepek ◽  
Christine Mannhalter ◽  
Jurgen Krauter ◽  
Stefanie Hildenhagen ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Cord Blood ◽  
Acute Myelogenous Leukemia ◽  
Myelogenous Leukemia ◽  
Acute Myelogenous

scholarly journals Cytogenetic analysis of chimerism and leukemia relapse in chronic myelogenous leukemia patients after T cell-depleted bone marrow transplantation

Blood ◽  
1990 ◽  
Vol 75 (6) ◽  
pp. 1346-1355
Author(s):  
K Offit ◽  
JP Burns ◽  
I Cunningham ◽  
SC Jhanwar ◽  
P Black ◽  
...  
Keyword(s):  
Bone Marrow ◽  
T Cells ◽  
Bone Marrow Transplantation ◽  
T Cell ◽  
Marrow Transplantation ◽  
Myelogenous Leukemia ◽  
Host Cells ◽  
Clinical Relapse ◽  
Cytogenetic Studies ◽  
Ph Chromosome

Serial cytogenetic studies were performed on 64 patients with chronic myelogenous leukemia (CML) after T cell-depleted allogeneic bone marrow transplantation (BMT). Forty patients with CML in chronic phase (CP) received cytoreduction followed by BMT with HLA-matched T cell-depleted allogeneic marrow. The remaining 24 patients were transplanted in second chronic, accelerated, or blastic phase, or received T cell- depleted grafts with a dose of T cells added back. The Y chromosome and autosomal heteromorphisms were used to distinguish between donor and host cells. Mixed hematopoietic chimerism (presence of donor and host cells) was identified in 90% of patients in first CP. The Philadelphia (Ph) chromosome reappeared in 16 of the 40 first CP CML patients. As expected, patients who had detectable Ph chromosome positive cells at any time during the posttransplant period had a high likelihood of subsequent clinical relapse. Transient disappearance of the Ph positive clone was rarely observed, and was followed by reappearance of the Ph chromosome or clinical relapse. A subset of engrafted patients with greater than 25% host cells within 3 months post-BMT had a significantly shorter survival time free of cytogenetic or clinical relapse compared with other patients. In patients who had received donor T cells added to the T cell-depleted graft, there was a higher proportion of complete chimerism. Clonal progression of Ph positive as well as negative cells was observed and may be the result of radiation induced breakage. Serial cytogenetic studies of patients post-BMT can provide useful information regarding the biologic and clinical behavior of CML.

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