scholarly journals Epithelial Cell Regulation of Type 2 Cytokine Release by Peripheral Blood Mononuclear Cells

2020 ◽  
Author(s):  
Amy Southern ◽  
Aurelia Gondrand ◽  
Scott Layzell ◽  
Jennifer L Cane ◽  
Ian D Pavord ◽  
...  
Keyword(s):  
Epithelial Cell ◽  
Epithelial Cells ◽  
Mononuclear Cells ◽  
Cytokine Release ◽  
Peripheral Blood Mononuclear ◽  
Mechanical Disruption ◽  
Type 2 Cytokines ◽  
Epithelial Cell Lines ◽  
Blood Mononuclear Cells

AbstractBackgroundType 2 cytokines such as IL-13 and IL-5 are important drivers of pathophysiology and exacerbation in asthma. Defining how these type 2 cytokine responses are regulated is a research priority. Epithelial cells promote type 2 responses by releasing alarmins including IL-25, IL-33 and TSLP, but much less is known about inhibitory factors.MethodsIL-13 release was measured from peripheral blood mononuclear cells (PBMC) cultured with Interleukin (IL)-2 for five days. Epithelial cell lines or human bronchial epithelial cells (HBEC) isolated from healthy or asthma donors were added to these PBMC cultured with IL-2 and release of IL-13 or IL-5 measured. To characterise the mechanisms, we assessed the effect of mechanical disruption of epithelial cells, addition of the COX inhibitor indomethacin and the G-protein inhibitor pertussis toxin.ResultsPBMC cultured with IL-2 secreted type 2 cytokines in a cell number and time dependent manner. Epithelial cell lines inhibited IL-13 and IL-5 release after co-culture with PBMC in the presence of IL-2, directly, across a transwell and using epithelial cell supernatant. Cells or supernatant from HBEC from healthy or asthma donors also inhibited the cytokine release. Trypsin treatment of conditioned media indicated that inhibitory factor(s) are trypsin insensitive. Mechanical disruption of epithelial cells or indomethacin treatment had no effect, but pertussis toxin reduced epithelial cell inhibition of IL-2 driven type 2 cytokine release.ConclusionEpithelial cells regulate cytokine release by soluble factor(s) and this could be an important immunoregulatory function of the airway epithelium.

scholarly journals cAMP Activates The generation of Reactive Oxygen Species and Inhibits The Secretion of IL-6 in Peripheral Blood Mononuclear Cells from Type 2 Diabetic Patients

2009 ◽  
Vol 2 (5) ◽  
pp. 317-321 ◽  
Author(s):  
Camila Armond Isoni ◽  
Érica Abreu Borges ◽  
Clara Araújo Veloso ◽  
Rafael Teixeira Mattos ◽  
Miriam Martins Chaves ◽  
...  
Keyword(s):  
Reactive Oxygen Species ◽  
Peripheral Blood Mononuclear Cells ◽  
Peripheral Blood ◽  
Mononuclear Cells ◽  
Reactive Oxygen ◽  
Oxygen Species ◽  
Peripheral Blood Mononuclear ◽  
Blood Mononuclear Cells ◽  
In Cells

Peripheral blood mononuclear cells (PBMNC) from patients with type 2 diabetes (DM2) have generated higher levels of reactive oxygen species (ROS) that were higher than those in cells from healthy individuals. In the presence of a cAMP-elevating agent, ROS production was significantly activated in PBMNC from DM2 patients but it was inhibited in cells from healthy subjects. Higher levels of IL-6 has been detected in the supernatant of PBMNC cultures from DM2 patients in comparison with healthy controls. When cells were cultured in the presence of a cAMP-elevating agent, the level of IL-6 decreased has by 46% in the supernatant of PBMNC from DM2 patients but it remained unaltered in controls. No correlations between ROS and IL-6 levels in PBMNC from DM2 patients or controls have been observed. Secretions of IL-4 or IFN by PBMNC from patients or controls have not been affected by the elevation of cAMP. cAMP elevating agents have activated the production of harmful reactive oxidant down modulated IL-6 secretion by these cells from DM2 patients, suggesting an alteration in the metabolic response possibly due to hyperglicemia. The results suggest that cAMP may play an important role in the pathogenesis of diabetes.

scholarly journals Increased Expression of Tissue Factor and Receptor for Advanced Glycation End Products in Peripheral Blood Mononuclear Cells of Patients With Type 2 Diabetes Mellitus with Vascular Complications

2004 ◽  
Vol 5 (2) ◽  
pp. 163-169 ◽  
Author(s):  
A. E. Buchs ◽  
A. Kornberg ◽  
M. Zahavi ◽  
D. Aharoni ◽  
C. Zarfati ◽  
...  
Keyword(s):  
Type 2 Diabetes ◽  
Advanced Glycation End Products ◽  
Mononuclear Cells ◽  
Vascular Complications ◽  
Advanced Glycation ◽  
Peripheral Blood Mononuclear ◽  
Glycation End Products ◽  
End Products ◽  
Blood Mononuclear Cells

The aim of the study was to determine the correlation between the expression of tissue factor (TF) and the receptor for advanced glycation end products (RAGEs) and vascular complications in patients with longstanding uncontrolled type 2 diabetes (T2D). TF and RAGE mRNAs as well as TF antigen and activity were investigated in 21 T2D patients with and without vascular complications. mRNA expression was assessed by reverse transcriptase–polymerase chain reaction (RT-PCR) in nonstimulated and advanced glycation end product (AGE) albumin–stimulated peripheral blood mononuclear cells (PBMCs). TF antigen expression was determined by enzyme-linked immunosorbent assay (ELISA) and TF activity by a modified prothrombin time assay. Basal RAGE mRNA expression was 0.2 ± 0.06 in patients with complications and 0.05 ± 0.06 patients without complications (P= .004). Stimulation did not cause any further increase in either group. TF mRNA was 0.58 ± 0.29 in patients with complications and 0.21 ± 0.18 in patients without complications (P= .003). Stimulation resulted in a nonsignificant increase in both groups. Basal TF activity (U/106PBMCs) was 18.4 ± 13.2 in patients with complications and 6.96 ± 5.2 in patients without complications (P= .003). It increased 3-fold in both groups after stimulation (P= .001). TF antigen (pg/106PBMCs) was 33.7 ± 28.6 in patients with complications, 10.4 ± 7.8 in patients without complications (P= .02). Stimulation tripled TF antigen in both groups of patients (P= .001). The RAGE/TF axis is up-regulated inT2Dpatients with vascular complications as compared to patients without complications. This suggests a role for this axis in the pathogenesis of vascular complications in T2D.

scholarly journals Baseline interleukin1beta expression in peripheral blood monocytes predicts the extent of weight loss and nonalcoholic fatty liver improvement in obese subjects with prediabetes or type 2 diabetes

2020 ◽  
Vol 41 (Supplement_2) ◽  
Author(s):  
P.G Simeone ◽  
S Costantino ◽  
R Tripaldi ◽  
R Liani ◽  
S Ciotti ◽  
...  
Keyword(s):  
Weight Loss ◽  
Peripheral Blood ◽  
Receptor Agonist ◽  
Mononuclear Cells ◽  
Lifestyle Changes ◽  
Funding Source ◽  
Peripheral Blood Mononuclear ◽  
Blood Mononuclear Cells ◽  
Obese Subjects

Abstract Background Non-alcoholic fatty liver disease (NAFLD) represents a hallmark of metabolic syndrome. Interleukin-1β (IL-1β), a well-studied cytokine involved in obesity-related systemic inflammation as well as in the pathogenesis of type 2 diabetes (T2D), promotes hepatic steatosis by stimulating triglycerides and cholesterol accumulation in primary liver hepatocytes and lipid droplets formation. The most compelling evidence for a major role for IL-1β in metabolic imbalance and inflammation comes from the recent Canakinumab Anti-inflammatory Thrombosis Outcome (CANTOs)trial, where inhibition of IL-1β pathway was associated with a reduction of cardiovascular events in high-risk patients. Purpose The present study was designed to determine: i)whether an equal degree of weight loss by liraglutide or lifestyle changes has a different impact on NAFLD extent and IL-1β expression in peripheral blood mononuclear cells from obese subjects with prediabetes or early T2D; ii)whether baseline IL-1β levels may predict the extent of weight loss and related metabolic changes. Methods Thirty-two metformin-treated obese subjects with prediabetes [impaired fasting glucose (IFG) or impaired glucose tolerance (IGT) or both (n=16)] or newly diagnosed T2D (n=16), were randomized to the glucagon-like peptide receptor agonist (GLP-RA) liraglutide (1.8 mg/d) or lifestyle counselling until achieving a modest and comparable weight loss (−7% of initial body weight). Visceral (VAT) and adipose tissue distribution were assessed by magnetic resonance. Gene expression of IL-1β in peripheral blood mononuclear cells was assessed by real time PCR. Results At baseline, IL-1β positively correlated to body mass index (BMI) (rho=0.421, p=0.016), fasting plasma glucose (rho=0.415, p=0.018), HbA1c (rho=0.349, p=0.050), VAT (rho=0.388, p=0.028), NAFLD (rho=0.454, p=0.009), platelet count (rho=0.510, p=0.003), chemerin (rho=0.455, p=0.009) and interleukin-1 receptor agonist (IL1-RA) (rho=0.519, p=0.002). After achievement of the weight loss target in the two groups, a comparable reduction of IL-1 β (p<0.001 lifestyle changes; p=0.029 liraglutide treatment) was observed in both arms, in parallel with a comparable improvement in glycaemic control, C-reactive protein (CRP),BMI and NAFLD. Furthermore, basal levels of IL-1β correlated directly with delta BMI (p=0.015) and delta NAFLD (p=0.002) (Figure 1). Conclusion In obese patients with initial impairment of glucose metabolism, IL-β-driven inflammation correlates with glycaemic control, adipose tissue distribution and platelet count. Successful weight loss, achieved with either lifestyle changes or an incretin-based therapy, is associated with a significant reduction of both IL-1β levels and NAFLD degree. Of interest, basal levels of IL-1β predicts the extent of weight loss and NAFLD improvement, regardless of the intervention. Our results may set the stage for ad-hoc studies investigating the usefulness of baseline IL-1β a levels as a drug-response biomarker. Figure 1 Funding Acknowledgement Type of funding source: Public Institution(s). Main funding source(s): This study was supported by a grant from the Italian Ministry of University and Research (PRIN no. 2010JS3PMZ to F.S.).

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