Human aging is associated with altered TNF-α production during hyperglycemia and hyperinsulinemia

2001 ◽  
Vol 281 (6) ◽  
pp. E1137-E1143 ◽  
Author(s):  
John P. Kirwan ◽  
Raj K. Krishnan ◽  
James A. Weaver ◽  
Luis F. Del Aguila ◽  
William J. Evans
Keyword(s):  
Glucose Metabolism ◽  
Insulin Action ◽  
Mononuclear Cells ◽  
Ex Vivo ◽  
Normal Glucose Tolerance ◽  
Peripheral Blood Mononuclear ◽  
Significant Group ◽  
Hyperglycemic Clamp ◽  
Tnf Α ◽  
Factor Α

Changes in tumor necrosis factor-α (TNF-α) may provide a mechanism to explain impaired glucose metabolism with advancing age. Hyperglycemic clamps (180 min, 10 mM) were performed on seven older [67 ± 2 yr; body mass index (BMI) 24.7 ± 1.0 kg/m2] and seven younger (22 ± 1 yr; BMI 21.8 ± 1.3 kg/m2) healthy sedentary males with normal glucose tolerance. TNF-α production at basal and at the end of 180 min of hyperglycemia and hyperinsulinemia was measured ex vivo from lipopolysaccharide-stimulated (1 ng/ml) peripheral blood mononuclear cells. Plasma glucose, insulin, and C-peptide levels were similar in both groups at basal and during the last 30 min of the hyperglycemic clamp. Glucose infusion rates were lower ( P < 0.004) in the older group compared with the young, indicating decreased insulin action among the older subjects. Basal TNF-α secretion was similar in older and younger subjects. TNF-α was suppressed ( P < 0.02) in the younger group (230 ± 46 vs. 126 ± 49 pg/ml; basal vs. clamp) but not in the older group (153 ± 37 vs. 182 ± 42 pg/ml), with significant group differences in response ( P < 0.05). A significant correlation was observed between the level of suppression in TNF-α production and insulin action (Kendall's rank, τ = 0.40, P < 0.05). Furthermore, the TNF-α response during the clamp was related to fat mass ( r = 0.88, P < 0.001) and abdominal fat ( r = 0.81, P < 0.003). In conclusion, these findings suggest a possible mechanism by which TNF-α may modulate glucose metabolism in younger people. Aging and modest increases in adiposity prevent the “normal” suppression of TNF-α production after a sustained postprandial-like hyperglycemic-hyperinsulinemic stimulus, which may contribute in part to the decline in insulin sensitivity in older men.

scholarly journals Effect of soluble interleukin-6 receptor α and interleukin-6 secreted by polymorphonuclear leukocytes on tumor necrosis factor-α expression and its production by peripheral blood mononuclear cells

2002 ◽  
Vol 11 (5) ◽  
pp. 325-328 ◽  
Author(s):  
E. Jablonska
Keyword(s):  
Interleukin 6 ◽  
Polymorphonuclear Leukocytes ◽  
Tumor Necrosis ◽  
Tumor Necrosis Factor Α ◽  
Mononuclear Cells ◽  
Peripheral Blood Mononuclear ◽  
Tnf Α ◽  
Interleukin 6 Receptor ◽  
Factor Α ◽  
Necrosis Factor

Background: It has recently been shown that soluble interleukin-6 receptor (sIL-6R) alone or complexed with interleukin (IL)-6, besides their regulatory role in a wide variety of both normal and abnormal biologic reactions mediated by IL-6, could be an effective stimulator of the cell function.Aims: The key question of the present study is whether the sIL-6Rα or sIL-6R with IL-6 released by polymorphonuclear leukocytes (PMN) can influence cytokine secretion such as tumor necrosis factor-α (TNF-α) by peripheral blood mononuclear cells (PBMC), which together with PMN develop the inflammatory and immune response of a host.Methods: Cells were isolated from heparinized whole blood of healthy persons. The PMN were cultured for 1 h at 37°C in 5% CO2. After incubation, the culture supernatant of PMN was removed and was added to PBMC. The PBMC were cultured for 1 h at 37°C in the same conditions. In the culture supernatants and lysates of PMN, we examined the concentrations of sIL-6R by enzyme-linked immunosorbent assay (ELISA). TNF-α was measured at both protein and mRNA levels. Protein levels were determined by ELISA. To examine TNF-α mRNA expression, we isolated mRNA from PBMC after culture, using TRIZOL Reagent. The quantity of mRNA TNF-α was determined by the Quantikine mRNA assay.Results and conclusion: The results obtained revealed that sIL-6R with IL-6 secreted by PMN may play a regulatory role in the immune response by modulating the TNF-α expression and its production by PBMC. This may have a significant influence on an early phase of the inflammation and other reactions mediated by TNF-α.

scholarly journals Low Induction of Proinflammatory Cytokines Parallels Evolutionary Success of Modern Strains within the Mycobacterium tuberculosis Beijing Genotype

2013 ◽  
Vol 81 (10) ◽  
pp. 3750-3756 ◽  
Author(s):  
Arjan van Laarhoven ◽  
Jornt J. Mandemakers ◽  
Johanneke Kleinnijenhuis ◽  
Mimount Enaimi ◽  
Ekta Lachmandas ◽  
...  
Keyword(s):  
Mycobacterium Tuberculosis ◽  
Mononuclear Cells ◽  
Ex Vivo ◽  
Selective Advantage ◽  
Beijing Genotype ◽  
Peripheral Blood Mononuclear ◽  
Content Type ◽  
Tnf Α ◽  
Evolutionary Success ◽  
Ifn Γ

ABSTRACTOne of the most widespread clades ofMycobacterium tuberculosisworldwide, the Beijing genotype family, consists of ancient (atypical) and modern (typical) strains. Modern Beijing strains outcompete ancient strains in terms of prevalence, while reserving a higher degree of genetic conservation. We hypothesize that their selective advantage lies in eliciting a different host immune response. Bead-disrupted lysates of a collection of differentM. tuberculosisstrains of the modern (n= 7) or ancient (n= 7) Beijing genotype, as well as the Euro-American lineage (n= 6), were used for induction ofex vivocytokine production in peripheral blood mononuclear cells (PBMCs) from 10 healthy individuals. Hierarchical clustering and multivariate regression analyses were used to study possible differences in production of nine cytokines. Modern and ancientM. tuberculosisBeijing genotypes induced different cytokine signatures. Overall induction of interleukin-1β (IL-1β), gamma interferon (IFN-γ), and IL-22 was 38 to 40% lower after stimulation with modern Beijing strains (correctedPvalues of <0.0001, 0.0288, and 0.0002, respectively). Euro-American reactivation strains induced 2-fold more TNF-α production than both types of Beijing strains. The observed differences in cytokine induction point to a reduction in proinflammatory cytokine response as a possible contributing factor to the evolutionary success of modern Beijing strains.

scholarly journals Identification of Different Extracellular Vesicles in the Hydatid Fluid of Echinococcus granulosus and Immunomodulatory Effects of 110 K EVs on Sheep PBMCs

2021 ◽  
Vol 12 ◽  
Author(s):  
Jing Yang ◽  
Jin'en Wu ◽  
Yong Fu ◽  
Lujun Yan ◽  
Yating Li ◽  
...  
Keyword(s):  
Echinococcus Granulosus ◽  
Extracellular Vesicles ◽  
Mononuclear Cells ◽  
Neglected Tropical Diseases ◽  
Dependent Manner ◽  
Peripheral Blood Mononuclear ◽  
Hydatid Fluid ◽  
Tnf Α ◽  
Factor Α ◽  
Host Parasite

Echinococcosis, mainly caused by Echinococcus granulosus, is one of the 17 neglected tropical diseases. Extracellular vesicles (EVs) play an essential role in the host–parasite interplay. However, the EVs in the hydatid fluid (HF) of E. granulosus are not fully characterized. Herein, three different types of HF EVs, designated as 2 K, 10 K, and 110 K EVs based on the centrifugal force used, were morphologically identified. A total of 97, 80, and 581 proteins were identified in 2 K, 10 K, and 110 K EVs, respectively, 39 of which were commonly shared. Moreover, 11, 8, and 25 miRNAs were detected, respectively, and all of the 7 selected miRNAs were validated by qPCR to be significantly lower abundant than that in protoscoleces. It was further deemed that 110 K EVs were internalized by sheep peripheral blood mononuclear cells (PBMCs) in a time-dependent manner and thus induced interleukin (IL)-10, tumor necrosis factor-α (TNF-α), and IRF5 were significantly upregulated and IL-1β, IL-17, and CD14 were significantly downregulated (p &lt; 0.05). These data demonstrate the physical discrepancy of three HF EVs and an immunomodulatory effect of 110 K EVs on sheep PMBCs, suggesting a role in immune responses during E. granulosus infection.

"Tien-Hsien Liquid" Can Modulate Antigen-Stimulated Cytokine Production by T-Cells Isolated from Patients with Recurrent Aphthous Ulcerations

2005 ◽  
Vol 33 (04) ◽  
pp. 559-571 ◽  
Author(s):  
Andy Sun ◽  
Jean-San Chia ◽  
Won-Bo Wang ◽  
Chun-Pin Chiang
Keyword(s):  
T Cells ◽  
Mononuclear Cells ◽  
Cytokine Production ◽  
Interferon Γ ◽  
Enzyme Linked Immunosorbent Assay ◽  
Peripheral Blood Mononuclear ◽  
Tnf Α ◽  
Ifn Γ ◽  
Factor Α ◽  
Necrosis Factor

Recurrent aphthous ulcerations (RAU) represent a common oral mucosal disease with altered humoral and cellular immunities. Tien-Hsien liquid (THL) is an extract of Chinese medicinal herbs with immunomodulating effects. Our previous study found that THL can modulate the antigen-stimulated proliferative response of peripheral blood mononuclear cells and T-cells isolated from RAU patients. In this study, we further tested whether THL can modulate the antigen-stimulated cytokine production by T-cells isolated from RAU patients. To achieve this goal, T-cells isolated from 19 RAU patients were incubated with phytohemagglutinin (PHA), glutaraldehyde-inactivated tetanus toxoid (TT), glucosyltransferase D (GtfD), or antigens of Streptococcus mutans in the presence or absence of THL. The levels of interleukin (IL)-2, interferon-γ (IFN-γ), tumor necrosis factor-α (TNF-α), IL-6, or IL-10 in the supernatants of T-cell cultures were measured by cytokine enzyme-linked immunosorbent assay (ELISA) kits. We found that THL significantly increased the PHA- or TT-stimulated TNF-α, IL-6, and IL-10 production by T-cells isolated from RAU patients. However, THL could also significantly decrease the TT-stimulated IL-2 production, the GtfD-stimulated IL-2, TNF-α, IL-6 and IL-10 production, and the S. mutans-stimulated IFN-γ, TNF-α, and IL-10 production by T-cells isolated from RAU patients. These results indicate that THL can modulate the antigen-stimulated cytokine production by T-cells isolated from RAU patients. Because RAU is probably a Thl-mediated disease with elevated levels of IL-2, IFN-γ, TNF-α and IL-6 in either the patient's sera or oral lesions and these increased levels of cytokines can be reduced by THL, we suggest that THL may be a potential immunoceutical agent for treatment of RAU.

Silver nanoparticles augment releasing of pyrogenic factors by blood cells stimulated with LPS

2014 ◽  
Vol 9 (11) ◽  
pp. 1058-1067 ◽  
Author(s):  
Tomasz Jedrzejewski ◽  
Sylwia Wrotek ◽  
Jakub Piotrowski ◽  
Wieslaw Kozak
Keyword(s):  
Silver Nanoparticles ◽  
Motor Activity ◽  
Mononuclear Cells ◽  
Sickness Behavior ◽  
Interleukin 1Β ◽  
Peripheral Blood Mononuclear ◽  
Tnf Α ◽  
Factor Α ◽  
The Impact ◽  
Necrosis Factor

AbstractSilver nanoparticles (AgNPs) have cytotoxic properties via generation of reactive oxygen species which are involved in the generalized sickness behavior of the host, including fever and lethargy among others. The aim of the present study was to investigate the impact of AgNPs on the ability of rat peripheral blood mononuclear cells (PBMCs) to release fever mediating factors after stimulation with lipopolysaccharide (LPS). Body temperature and motor activity of the Wistar rats were measured by biotelemetry system. Rat PBMCs were stimulated with LPS and after that the cells were washed and incubated alone or with AgNPs. The final supernatants were injected intraperitoneally. The levels of endogenous pyrogens such as interleukin-1β (IL−1β), IL-6 and tumor necrosis factor-α (TNF-α) released from the PBMCs into the final supernatants were also estimated. The results indicated that injection of the supernatants from the cells stimulated with LPS induced fever and inhibited motor activity. These effects were potentiated by the presence of AgNPs during the final incubation. The presence of the AgNPs also resulted in significant increases in levels of endogenous pyrogens. The augmentation of fever in the rats by the AgNPs treatment of the cultures seemed to be primarily associated with the changes in interleukin-1β levels.

scholarly journals Longevity-Associated Variant of BPIFB4 Mitigates Monocyte-Mediated Acquired Immune Response

2019 ◽  
Vol 74 (Supplement_1) ◽  
pp. S38-S44 ◽  
Author(s):  
Elena Ciaglia ◽  
Francesco Montella ◽  
Anna Maciag ◽  
Pasqualina Scala ◽  
Anna Ferrario ◽  
...  
Keyword(s):  
Mononuclear Cells ◽  
Therapeutic Potential ◽  
Human Monocyte ◽  
Peripheral Blood Mononuclear ◽  
Inflammatory Status ◽  
Tnf Α ◽  
Cytokine Tumor Necrosis Factor ◽  
Pkc Alpha ◽  
Factor Α ◽  
Necrosis Factor

Abstract One of the basis of exceptional longevity is the maintaining of the balance between inflammatory and anti-inflammatory networks. The monocyte-macrophages activation plays a major role in tuning the immune responses, by oscillating between patrolling-protective to inflammatory status. Longevity-associated variant (LAV) of bactericidal/permeability-increasing fold-containing family B member 4 (BPIFB4) activates calcium, PKC-alpha, and eNOS, rescuing endothelial dysfunction in aged mice and inducing revascularization. The BPIFB4’s increment in serum of healthy long-living individuals (LLIs) compared to nonhealthy ones, its therapeutic potential in improving vascular homeostasis, which depends on immune system, together with its expression in bone marrow myeloid cells, suggests that LAV-BPIFB4 may improve immune regulation. Here we show that human monocytes exposed to LAV-BPIFB4 protein increased co-stimulatory molecules in resting state and reduced pro-inflammatory cytokine tumor necrosis factor-α (TNF-α) and interleukin-1β (IL-1β) after activating stimuli. Accordingly, a low percentage of CD69+ activated lymphocytes are found among LAV-BPIFB4-treated peripheral blood mononuclear cells (PBMCs). Moreover, human monocyte-derived dendritic cells (DCs) generated in presence of LAV-BPIFB4 secreted higher anti-(IL-10 and TGF-β) and lower pro-inflammatory (TNF-α and IL-1β) cytokines. Accordingly, LLIs’ plasma showed higher levels of circulating IL-10 and of neutralizing IL-1 receptor antagonist (IL-1RA) compared to controls. Thus, LAV-BPIFB4 effects on myeloid compartment could represent one example of a genetic predisposition carried by LLIs to protect from immunological dysfunctions.

scholarly journals The Staphyloccous aureus Eap Protein Activates Expression of Proinflammatory Cytokines

2008 ◽  
Vol 76 (5) ◽  
pp. 2164-2168 ◽  
Author(s):  
Thomas J. Scriba ◽  
Sophie Sierro ◽  
Eric L. Brown ◽  
Rodney E. Phillips ◽  
Andrew K. Sewell ◽  
...  
Keyword(s):  
Proinflammatory Cytokines ◽  
Mononuclear Cells ◽  
Ex Vivo ◽  
Human Peripheral Blood ◽  
Intercellular Adhesion Molecule ◽  
Intercellular Adhesion Molecule 1 ◽  
Peripheral Blood Mononuclear ◽  
Necrosis Factor Alpha ◽  
Tnf Α ◽  
Monocytes And Macrophages

ABSTRACT The extracellular adhesion protein (Eap) secreted by the major human pathogen Staphylococcus aureus is known to have several effects on human immunity. We have recently added to knowledge of these roles by demonstrating that Eap enhances interactions between major histocompatibility complex molecules and human leukocytes. Several studies have indicated that Eap can induce cytokine production by human peripheral blood mononuclear cells (PBMCs). To date, there has been no rigorous attempt to identify the breadth of cytokines produced by Eap stimulation or to identify the cell subsets that respond. Here, we demonstrate that Eap induces the secretion of the proinflammatory cytokines interleukin 6 (IL-6) and tumor necrosis factor alpha (TNF-α) by CD14+ leukocytes (monocytes and macrophages) within direct ex vivo PBMC populations (note that granulocytes are also CD14+ but are largely depleted from PBMC preparations). Anti-intercellular adhesion molecule 1 (CD54) antibodies inhibited this induction and implicated a role for this known Eap binding protein in cellular activation. IL-6 and TNF-α secretion by murine cells exposed to Eap was also observed. The activation of CD14+ cells by Eap suggests that it could play a significant role in both septic shock and fever, two of the major pathological features of S. aureus infections.

scholarly journals Vitamin D Receptor Down-Regulation Is Associated With Severity of Albuminuria in Type 2 Diabetes Patients

2016 ◽  
Vol 101 (11) ◽  
pp. 4395-4404 ◽  
Author(s):  
Bin Yi ◽  
Jing Huang ◽  
Wei Zhang ◽  
Ai Mei Li ◽  
Shi Kun Yang ◽  
...  
Keyword(s):  
Type 2 Diabetes ◽  
Vitamin D ◽  
Vitamin D Receptor ◽  
Mononuclear Cells ◽  
Ex Vivo ◽  
Down Regulation ◽  
Peripheral Blood Mononuclear ◽  
Tnf Α ◽  
Hk2 Cells

Context: Inflammation plays an important role in albuminuria in type 2 diabetes mellitus (T2DM). The vitamin D receptor (VDR) has potent anti-inflammatory activities. Objective: To investigate the correlation between VDR expression and albuminuria in T2DM. Design/Setting/Patients: Renal biopsies from T2DM patients with albuminuria (n = 8) and nondiabetic subjects (n = 4) were compared for VDR expression by immunohistochemistry. Recruited T2DM patients (n = 242; estimated glomerular filtration rate &gt; 60 mL/min/1.73 m2) were divided into three groups based on urinary albumin-to-creatinine ratio (uACR): normal albuminuria (uACR &lt; 30 mg/g; n = 85), microalbuminuria (30 mg/g ≤ uACR &lt; 300 mg/g; n = 84), and macroalbuminuria (uACR ≥ 300 mg/g; n = 73), with healthy individuals (n = 72) as controls. Peripheral blood mononuclear cells (PBMCs) from these subjects were analyzed for VDR mRNA (n = 314), TNF-α mRNA (n = 314), microRNA (miR)-346 (n = 120; 30 for each group), and VDR protein (n = 80; 20 for each group). PBMCs from randomly selected subjects (n = 6 for each group) were cultured ex vivo to evaluate the effect of TNF-α on miR-346 and VDR, and miR-346-mediated VDR suppression was further explored in HK2 cells. Results: VDR expression was down-regulated in PBMCs and renal tubular epithelial cells from T2DM patients with albuminuria. VDR mRNA and protein levels were both negatively correlated with uACR, and VDR mRNA was inversely correlated with TNF-α and miR-346 in PBMCs from T2DM patients. TNF-α reduced VDR while inducing miR-346 in cultured PBMCs. TNF-α suppressed VDR by up-regulating miR-346 in HK2 cells. Conclusions: VDR down-regulation in PBMCs is independently associated with the severity of albuminuria in T2DM. TNF-α suppression of VDR in PBMCs and HK2 cells is mediated by miR-346.

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