scholarly journals The hUCMSCs Exerts Excellent Anti-inflammation Effect which is Different from TCZ IL-6 Antagonist by Inducing High IL-6 Secretion

2021 ◽  
Author(s):  
Huei-Yu Lo ◽  
Shun-Ping Cheng ◽  
Jing-Long Huang ◽  
Kuo-Ting Chang ◽  
Yu-Lung Chang ◽  
...  
Keyword(s):  
Microarray Data ◽  
Mononuclear Cells ◽  
Inhibitory Effect ◽  
Human Umbilical Cord ◽  
Gene Microarray ◽  
High Concentration ◽  
Peripheral Blood Mononuclear ◽  
Potent Inhibitory Effect ◽  
Anti Inflammation ◽  
Suppression Assay

Abstract BACKGROUND The biologic and cellular IL-6-related therapies have been used to treat the autoimmune diseases (AID), which prompting us to furtherly explore the IL-6 role in human umbilical cord mesenchymal stem cells (hUCMSCs) therapy.MATERIALS & METHODS Peripheral blood mononuclear cells (PBMCs) were responder co-cultured with hUCMSCs or exogenous IL-6. PBMC suppression assay was used to analyze the anti-inflammatory effects by using the MTT assay. The IL-6 concentration in supernatant was measured using ELISA. The correlation between anti-inflammation effect of hUCMSCs and IL-6 levels, and the relevant roles of IL-6, IL-6 mRNA expression was analyzed using the MetaCore functional network constructed from gene microarray data. The location of IL-6 and IL-6 receptor (IL-6R) expression was furtherly evaluated.RESULTS Initially, hUCMSCs did not exert any inhibitory effect on PBMCs, however, a potent inhibitory effect on PBMCs was observed and the IL-6 concentration reached about 1000 ng/mL after 72 hours. Exogenous 1000 ng/mL IL-6 could inhibit PBMCs inflammations but less than that of hUCMSCs. The hUCMSCs exerts excellent anti-inflammation effect by inducing higher IL-6 level which is different from TCZ IL-6 antagonistCONCLUSIONS High concentration IL-6 cytokine secretion plays an important role in the anti-inflammation effect of hUCMSCs cell therapy.

scholarly journals High Induction of IL-6 Secretion From hUCMSCs Optimize the Potential of hUCMSCs and TCZ as Therapy for COVID-19-Related ARDS

2021 ◽  
Vol 30 ◽  
pp. 096368972110544
Author(s):  
Huei-Yu Lo ◽  
Shun-Ping Cheng ◽  
Jing-Long Huang ◽  
Kuo-Ting Chang ◽  
Yu-Lung Chang ◽  
...  
Keyword(s):  
Mononuclear Cells ◽  
Therapeutic Potential ◽  
Neutralizing Antibody ◽  
Inhibitory Effect ◽  
Human Umbilical Cord ◽  
High Concentration ◽  
Peripheral Blood Mononuclear ◽  
Potent Inhibitory Effect ◽  
Anti Inflammatory ◽  
Inflammatory Effect

Biological and cellular interleukin-6 (IL-6)-related therapies have been used to treat severe COVID-19 pneumonia with hyperinflammatory syndrome and acute respiratory failure, which prompted further exploration of the role of IL-6 in human umbilical cord mesenchymal stem cell (hUCMSC) therapy. Peripheral blood mononuclear cells (PBMCs) were responders cocultured with hUCMSCs or exogenous IL-6. A PBMC suppression assay was used to analyze the anti-inflammatory effects via MTT assay. The IL-6 concentration in the supernatant was measured using ELISA. The correlation between the anti-inflammatory effect of hUCMSCs and IL-6 levels and the relevant roles of IL-6 and IL-6 mRNA expression was analyzed using the MetaCore functional network constructed from gene microarray data. The location of IL-6 and IL-6 receptor (IL-6R) expression was further evaluated. We reported that hUCMSCs did not initially exert any inhibitory effect on PHA-stimulated proliferation; however, a potent inhibitory effect on PHA-stimulated proliferation was observed, and the IL-6 concentration reached approximately 1000 ng/mL after 72 hours. Exogenous 1000 ng/mL IL-6 inhibited PHA-stimulated inflammation but less so than hUCMSCs. The inhibitory effects of hUCMSCs on PHA-stimulated PBMCs disappeared after adding an IL-6 neutralizing antibody or pretreatment with tocilizumab (TCZ), an IL-6R antagonist. hUCMSCs exert excellent anti-inflammatory effects by inducing higher IL-6 levels, which is different from TCZ. High concentration of IL-6 cytokine secretion plays an important role in the anti-inflammatory effect of hUCMSC therapy. Initial hUCMSC therapy, followed by TCZ, seems to optimize the therapeutic potential to treat COVID-19-related acute respiratory distress syndrome (ARDS).

scholarly journals In Vitro Effects of Olive Vegetation Water on IFN-γ and IL-10 Secretion in Multiple Sclerosis Patients

2021 ◽  
Vol 1 (1) ◽  
Author(s):  
Mahboubeh Baheri ◽  
Mohammadreza Dayer ◽  
Narges Baharifar ◽  
Abdolkarim Sheikhi ◽  
Abolfazl Sheikh
Keyword(s):  
Multiple Sclerosis ◽  
Mononuclear Cells ◽  
Inhibitory Effect ◽  
Inflammatory Disorder ◽  
Peripheral Blood Mononuclear ◽  
Inflammatory Reactions ◽  
Ifn Γ ◽  
Vegetation Water ◽  
Multiple Sclerosis Patients

Background: Multiple Sclerosis (MS) is an autoimmune and inflammatory disorder of the central nervous system (CNS), which is associated with the imbalance of pro- and anti-inflammatory cytokines. Evidence indicates that nutritional interventions have some immunomodulatory impacts. Objectives: In this study, we investigated the effect of olive vegetation water (OVW) on IFN-γ and IL-10 secretion by peripheral blood mononuclear cells (PBMCs) of MS patients. Methods: In this study, PBMCs of MS patients were separated by Ficoll-Hypaque centrifugation. The cytotoxicity of OVW was assessed by the MTT assay. The treatments were performed for 48 and 72 hours, and IFN-γ and IL-10 were measured by ELISA. Results: No cytotoxicity was observed for OVW. Besides, OVW showed a significant inhibitory effect on IFN-γ secretion but augmenting effect on IL-10 secretion by PBMCs dose-dependently. Conclusions: This study indicated that OVW could have immunoregulatory effects on inflammatory reactions in MS patients.

scholarly journals Inhibitory Effect of Glucocorticoid for Osteoblast Apoptosis Induced by Activated Peripheral Blood Mononuclear Cells

Endocrinology ◽  
1998 ◽  
Vol 139 (4) ◽  
pp. 2032-2040 ◽  
Author(s):  
Tomoki Nakashima ◽  
Hitoshi Sasaki ◽  
Masahiko Tsuboi ◽  
Atsushi Kawakami ◽  
Kaoru Fujiyama ◽  
...  
Keyword(s):  
Peripheral Blood Mononuclear Cells ◽  
Peripheral Blood ◽  
Mononuclear Cells ◽  
Inhibitory Effect ◽  
Peripheral Blood Mononuclear ◽  
Blood Mononuclear Cells ◽  
Osteoblast Apoptosis

scholarly journals Interleukin-4 inhibits indoleamine 2,3-dioxygenase expression in human monocytes

Blood ◽  
1994 ◽  
Vol 83 (5) ◽  
pp. 1408-1411 ◽  
Author(s):  
T Musso ◽  
GL Gusella ◽  
A Brooks ◽  
DL Longo ◽  
L Varesio
Keyword(s):  
Interferon Gamma ◽  
Mononuclear Cells ◽  
Inhibitory Effect ◽  
Interleukin 4 ◽  
Human Monocytes ◽  
Peripheral Blood Mononuclear ◽  
Ifn Gamma ◽  
Indoleamine 2,3 Dioxygenase ◽  
Blood Mononuclear Cells ◽  
Negative Signal

Abstract Indoleamine 2,3-dioxygenase (IDO), a flavin-dependent enzyme that catalyzes the conversion of tryptophan to kynurenine, is induced in peripheral blood mononuclear cells by interferon-gamma (IFN gamma). Interleukin-4 (IL-4) is a cytokine that modulates the functional properties of monocytes/macrophages, and we investigated the effects of IL-4 on IDO. We showed that IL-4 inhibited the induction of IDO mRNA and IDO activity by IFN gamma in human monocytes. The inhibitory effect was evident with as little as 2 U/mL of IL-4. These results provide the first evidence that a cytokine can provide a negative signal for IDO expression and that IL-4 can influence the catabolism of tryptophan.

The Effect of Acupuncture on Proinflammatory Cytokine Production in Patients with Chronic Headache: A Preliminary Report

2003 ◽  
Vol 31 (06) ◽  
pp. 945-954 ◽  
Author(s):  
Hyun-Ja Jeong ◽  
Seung-Heon Hong ◽  
Yong-Che Nam ◽  
Hee-Sook Yang ◽  
Yeoung-Su Lyu ◽  
...  
Keyword(s):  
Chronic Headache ◽  
Mononuclear Cells ◽  
Cytokine Production ◽  
Acupuncture Treatment ◽  
Clinical Signs ◽  
Inhibitory Effect ◽  
Acute Stage ◽  
Control Group ◽  
Peripheral Blood Mononuclear ◽  
Tnf Α

Acupuncture has been widely used as a treatment for various conditions like headache and stroke, especially in Asian countries such as Korea and China. But few scientific investigations have been carried out. The aim of the present study is to investigate the effect of acupuncture on the production of inflammatory cytokines in patients with chronic headache (CH). Patients with CH were treated with acupuncture during the acute stage. Clinical signs of CH disappeared markedly after three months of treatment with acupuncture. Peripheral blood mononuclear cells obtained from a normal group and those from the patients with CH, before and after treatment with acupuncture, were cultured for 24 hours in the presence or absence of lipopolysaccharide (LPS). The amount of interleukin (IL)-1β, IL-6 and tumor necrosis factor-α (TNF-α) in LPS culture supernatant was significantly increased in the patients with CH compared to the healthy control group (p < 0.05). But those cytokines came down toward the levels of the healthy group (p < 0.05) after treatment with acupuncture, although the levels still remained elevated. Plasma cytokine levels were analyzed to evaluate any change due to acupuncture treatment. There was little difference in the levels of IL-1β or IL-6 due to the treatment with acupuncture in the patients with CH, but significantly reduced plasma levels of TNF-α were observed. These data suggest that acupuncture treatment has an inhibitory effect on pro-inflammatory cytokine production in patients with CH.

Extracellular ubiquitin inhibits the TNF-α response to endotoxin in peripheral blood mononuclear cells and regulates endotoxin hyporesponsiveness in critical illness

Blood ◽  
2003 ◽  
Vol 101 (5) ◽  
pp. 1882-1890 ◽  
Author(s):  
Matthias Majetschak ◽  
Ulrich Krehmeier ◽  
Mark Bardenheuer ◽  
Christof Denz ◽  
Michael Quintel ◽  
...  
Keyword(s):  
Critical Illness ◽  
Peripheral Blood Mononuclear Cells ◽  
Inhibitory Activity ◽  
Mononuclear Cells ◽  
Inhibitory Effect ◽  
Trauma Patients ◽  
Peripheral Blood Mononuclear ◽  
Healthy Donors ◽  
Tnf Α ◽  
Blood Mononuclear Cells

Ubiquitin is suggested to play a key role in essential intracellular functions, such as heat shock response, protein breakdown, and regulation of immune responses. Ubiquitin has also been detected in the extracellular space, but the function and biologic significance is unclear. We describe a new function of extracellular ubiquitin and show that extracellular ubiquitin specifically inhibits ex vivo secretion of tumor necrosis factor-α (TNF-α) and TNF-α mRNA expression from peripheral blood mononuclear cells (PBMNCs) in response to endotoxin in a dose-dependent manner. In contrast, the TNF-α response to zymosan or Staphylococcus aureus as well as the interleukin-6 (IL-6) and IL-8 responses to endotoxin were unaffected by ubiquitin. Measurement of serum ubiquitin levels showed a significant 5- to 7-fold increase in sepsis and trauma patients, to the level required for inhibition of the PBMNC TNF-α response to endotoxin by ubiquitin. Elevated ubiquitin levels in serum were significantly correlated with a reduced TNF-α production. Antibodies to ubiquitin were able to (1) significantly increase (2- to 5-fold) the TNF-α response to endotoxin in whole blood from trauma and sepsis patients, (2) completely neutralize the inhibitory effect of trauma patients' serum on healthy donors' TNF-α production, and (3) partially neutralize the inhibitory effect of sepsis patients' serum on healthy donors' TNF-α production. Ubiquitin-depleted serum from trauma patients lost the inhibitory activity for TNF-α production, whereas extracted endogenous ubiquitin exerts the inhibitory activity. The results demonstrate that extracellular ubiquitin acts as a cytokinelike protein with anti-inflammatory properties and indicate that extracellular ubiquitin is involved in the regulation of immunodepression in critical illness.

Interleukin-10 Inhibits Erythropoietin-Independent Growth of Erythroid Bursts in Patients With Polycythemia Vera

Blood ◽  
1998 ◽  
Vol 92 (6) ◽  
pp. 1967-1972 ◽  
Author(s):  
Klaus Geissler ◽  
Leopold Öhler ◽  
Manuela Födinger ◽  
Eva Kabrna ◽  
Marietta Kollars ◽  
...  
Keyword(s):  
Polycythemia Vera ◽  
Mononuclear Cells ◽  
Mrna Level ◽  
Interleukin 10 ◽  
Inhibitory Effect ◽  
Colony Stimulating Factor ◽  
Peripheral Blood Mononuclear ◽  
Gm Csf ◽  
Stimulating Factor ◽  
Csf Production

Abstract In polycythemia vera (PV) erythroid colonies that grow in vitro in the absence of exogenous erythropoietin (EPO) arise from the abnormal clone that is responsible for overproduction of red blood cells. Although the mechanism of autonomous formation of burst-forming units-erythroid (BFU-E) is not fully understood, a spontaneous release of growth regulatory molecules by PV cells and/or by accessory cells is likely to be involved. Because of its cytokine synthesis inhibiting action, interleukin-10 (IL-10) could be a potentially useful molecule to modulate abnormal erythropoiesis in PV. We studied the effect of recombinant human IL-10 on the EPO-independent growth of erythroid bursts derived from peripheral blood mononuclear cells (PBMNCs) of patients with PV. IL-10 showed a profound, dose-dependent, and specific inhibitory effect on autonomous BFU-E formation. Ten nanograms per milliliter of IL-10 significantly suppressed spontaneous growth of erythroid colonies in methylcellulose in five of five PV patients tested with a mean inhibition by 81% (range, 72-94). To elucidate the possible mechanism of the inhibitory action of IL-10 we further studied the effect of anticytokine antibodies on autonomous BFU-E growth and the ability of exogenous cytokines to restore IL-10–induced suppression of erythroid colony growth. Among a panel of growth regulatory factors tested (granulocyte-macrophage colony-stimulating factor [GM-CSF], IL-3, granulocyte colony-stimulating factor, stem cell factor, and insulin-like growth factor-1) GM-CSF was the only molecule for which both an inhibition of spontaneous BFU-E formation by its respective antibody as well as a significant restimulation of erythroid colonies in IL-10-treated cultures by exogenous addition was found. Moreover, inhibition of GM-CSF production by IL-10 was shown in PV PBMNCs at the mRNA level. Our data indicate that autonomous BFU-E growth in PV can be profoundly inhibited by IL-10 and that this inhibitory effect seems to be at least in part secondary to suppression of endogenous GM-CSF production. © 1998 by The American Society of Hematology.

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