scholarly journals Endothelial cell apicobasal polarity coordinates distinct responses to luminally versus abluminally delivered TNF-α in a microvascular mimetic

2020 ◽  
Vol 12 (11) ◽  
pp. 275-289
Author(s):  
Alec T Salminen ◽  
Jeffrey Tithof ◽  
Yara Izhiman ◽  
Elysia A Masters ◽  
Molly C McCloskey ◽  
...  
Keyword(s):  
Inflammatory Cytokines ◽  
Systemic Inflammation ◽  
Polymorphonuclear Neutrophil ◽  
Apical Surface ◽  
Necrosis Factor Alpha ◽  
Apicobasal Polarity ◽  
Tnf Α ◽  
Luminal Side ◽  
Cytokine Tumor Necrosis Factor ◽  
Key Barrier

Abstract Endothelial cells (ECs) are an active component of the immune system and interact directly with inflammatory cytokines. While ECs are known to be polarized cells, the potential role of apicobasal polarity in response to inflammatory mediators has been scarcely studied. Acute inflammation is vital in maintaining healthy tissue in response to infection; however, chronic inflammation can lead to the production of systemic inflammatory cytokines and deregulated leukocyte trafficking, even in the absence of a local infection. Elevated levels of cytokines in circulation underlie the pathogenesis of sepsis, the leading cause of intensive care death. Because ECs constitute a key barrier between circulation (luminal interface) and tissue (abluminal interface), we hypothesize that ECs respond differentially to inflammatory challenge originating in the tissue versus circulation as in local and systemic inflammation, respectively. To begin this investigation, we stimulated ECs abluminally and luminally with the inflammatory cytokine tumor necrosis factor alpha (TNF-α) to mimic a key feature of local and systemic inflammation, respectively, in a microvascular mimetic (μSiM-MVM). Polarized IL-8 secretion and polymorphonuclear neutrophil (PMN) transmigration were quantified to characterize the EC response to luminal versus abluminal TNF-α. We observed that ECs uniformly secrete IL-8 in response to abluminal TNF-α and is followed by PMN transmigration. The response to abluminal treatment was coupled with the formation of ICAM-1-rich membrane ruffles on the apical surface of ECs. In contrast, luminally stimulated ECs secreted five times more IL-8 into the luminal compartment than the abluminal compartment and sequestered PMNs on the apical EC surface. Our results identify clear differences in the response of ECs to TNF-α originating from the abluminal versus luminal side of a monolayer for the first time and may provide novel insight into future inflammatory disease intervention strategies.

scholarly journals The Role of TNF-α and Anti-TNF-α Agents during Preconception, Pregnancy, and Breastfeeding

2021 ◽  
Vol 22 (6) ◽  
pp. 2922
Author(s):  
Katarzyna Romanowska-Próchnicka ◽  
Anna Felis-Giemza ◽  
Marzena Olesińska ◽  
Piotr Wojdasiewicz ◽  
Agnieszka Paradowska-Gorycka ◽  
...  
Keyword(s):  
Inflammatory Cytokines ◽  
First Trimester ◽  
Endocrine Function ◽  
Necrosis Factor Alpha ◽  
Hormone Synthesis ◽  
Migratory Activity ◽  
Immune System Diseases ◽  
Tnf Α ◽  
The Impact ◽  
In Pregnancy

Tumor necrosis factor-alpha (TNF-α) is a multifunctional Th1 cytokine and one of the most important inflammatory cytokines. In pregnancy, TNF-α influences hormone synthesis, placental architecture, and embryonic development. It was also shown that increased levels of TNF-α are associated with pregnancy loss and preeclampsia. Increased TNF-α levels in complicated pregnancy draw attention to trophoblast biology, especially migratory activity, syncytialisation, and endocrine function. Additionally, elevated TNF-α levels may affect the maternal-fetal relationship by altering the secretory profile of placental immunomodulatory factors, which in turn affects maternal immune cells. There is growing evidence that metabolic/pro-inflammatory cytokines can program early placental functions and growth in the first trimester of pregnancy. Furthermore, early pregnancy placenta has a direct impact on fetal development and maternal immune system diseases that release inflammatory (e.g., TNF-α) and immunomodulatory factors, such as chronic inflammatory rheumatic, gastroenterological, or dermatological diseases, and may result in an abnormal release of cytokines and chemokines in syncytiotrophoblasts. Pregnancy poses a challenge in the treatment of chronic disease in patients who plan to have children. The activity of the disease, the impact of pregnancy on the course of the disease, and the safety of pharmacotherapy, including anti-rheumatic agents, in pregnancy should be considered.

scholarly journals Age and Sport Intensity-Dependent Changes in Cytokines and Telomere Length in Elite Athletes

Antioxidants ◽  
2021 ◽  
Vol 10 (7) ◽  
pp. 1035
Author(s):  
Maha Sellami ◽  
Shamma Al-muraikhy ◽  
Hend Al-Jaber ◽  
Hadaia Al-Amri ◽  
Layla Al-Mansoori ◽  
...  
Keyword(s):  
Immune Response ◽  
Telomere Length ◽  
Inflammatory Cytokines ◽  
Elite Athletes ◽  
Age Groups ◽  
Moderate Intensity ◽  
Necrosis Factor Alpha ◽  
Blood Samples ◽  
Tnf Α ◽  
Anti Inflammatory

Background: Exercise-associated immune response plays a crucial role in the aging process. The aim of this study is to investigate the effect of sport intensity on cytokine levels, oxidative stress markers and telomere length in aging elite athletes. Methods: In this study, 80 blood samples from consenting elite athletes were collected for anti-doping analysis at an anti-doping laboratory in Italy (FMSI). Participants were divided into three groups according to their sport intensity: low-intensity skills and power sports (LI, n = 18); moderate-intensity mixed soccer players (MI, n = 31); and high-intensity endurance sports (HI, n = 31). Participants were also divided into two age groups: less than 25 (n = 45) and above 25 years old (n = 35). Serum levels of 10 pro and anti-inflammatory cytokines and two antioxidant enzymes were compared in age and sport intensity groups and telomere lengths were measured in their respective blood samples. Results: Tumor necrosis factor-alpha (TNF-α) was the only cytokine showing significantly higher concentration in older athletes, regardless of sport intensity. Interleukin (IL)-10 increased significantly in HI regardless of age group, whereas IL-6 concentration was higher in the older HI athletes. IL-8 showed a significant interaction with sport intensity in different age groups. Overall, significant positive correlations among levels of IL-6, IL-10, IL-8 and TNF-α were identified. The antioxidant catalase activity was positively correlated with levels of TNF-α. Telomere length increased significantly with sport intensity, especially in the younger group. Conclusion: HI had longer telomeres and higher levels of pro- and anti-inflammatory cytokines, suggesting less aging in HI compared to low and moderate counterparts in association with heightened immune response. Investigation of the functional significance of these associations on the health and performance of elite athletes is warranted.

scholarly journals Nutritional Value and Anti-inflammation Activity of Misutkaru with Added Gryllus bimaculatus Powder

2021 ◽  
Vol 19 (3) ◽  
pp. 467-476
Author(s):  
Jung-Soon Han
Keyword(s):  
Amino Acid ◽  
Inflammatory Cytokines ◽  
Nutritional Value ◽  
Interleukin 1 ◽  
Raw 264.7 Cells ◽  
Raw 264.7 ◽  
Gryllus Bimaculatus ◽  
Necrosis Factor Alpha ◽  
Automatic Amino Acid Analyzer ◽  
Tnf Α

Purpose: This study investigated the nutritional value of Misutkaru with added Gryllus bimaculatus powder (GBM) and its applicability as a healthy functional food.Methods: Chemical analysis of the moisture, crude fat, protein, and mineral contents was performed in accordance with the Association of Official Analytical Chemists (AOAC) guidelines. The amino acid and fatty acid compositions were analyzed using an automatic amino acid analyzer and gas chromatography, respectively. The levels of inflammatory cytokines tumor necrosis factor‑alpha (TNF-α), interleukin 1 beta (IL-1β), and interleukin 6 (IL‑6) induced by lipopolysaccharides in RAW 264.7 cells were measured.Results: The general composition per 100 g of GBM was 41.87 g protein, 19.75 g fat, and 28.52 g carbohydrates. The mineral content per 100 g of GBM was 889.66 mg calcium, 1189.73 mg potassium, 220.36 mg magnesium, 207.51 mg sodium, 694.81 mg phosphorus, and 15.50 mg zinc. In particular, valine (21.361 mg/kg), leucine (29.180 mg/kg), and isoleucine (15.562 mg/kg) were abundant in GBM. GBM also effectively downregulated the production of the inflammatory cytokines TNF-α, IL-1β, and IL-6 in RAW 264.7 macrophages.Conclusion: Misutkaru with added Gryllus bimaculatus powder may have potential for application in the development of food materials or foods to prevent muscle loss in elderly individuals and sarcopenia patients, build muscle, and prevent increase in blood lipid concentrations in middle aged people. In particular, as Gryllus bimaculatus is low in fat and carbohydrates, it can be used as a diet material.

scholarly journals Matrix Metalloproteinases Contribute to Brain Damage in Experimental Pneumococcal Meningitis

2000 ◽  
Vol 68 (2) ◽  
pp. 615-620 ◽  
Author(s):  
Stephen L. Leib ◽  
David Leppert ◽  
John Clements ◽  
Martin G. Täuber
Keyword(s):  
Matrix Metalloproteinases ◽  
Bacterial Meningitis ◽  
Brain Damage ◽  
Neuronal Injury ◽  
Housekeeping Gene ◽  
Close Correlation ◽  
Necrosis Factor Alpha ◽  
Mmp Inhibitor ◽  
Tnf Α ◽  
Cytokine Tumor Necrosis Factor

ABSTRACT The present study was performed to evaluate the role of matrix metalloproteinases (MMP) in the pathogenesis of the inflammatory reaction and the development of neuronal injury in a rat model of bacterial meningitis. mRNA encoding specific MMPs (MMP-3, MMP-7, MMP-8, and MMP-9) and the inflammatory cytokine tumor necrosis factor alpha (TNF-α) were significantly (P< 0.04) upregulated, compared to the β-actin housekeeping gene, in cortical homogenates at 20 h after infection. In parallel, concentrations of MMP-9 and TNF-α in cerebrospinal fluid (CSF) were significantly increased in rats with bacterial meningitis compared to uninfected animals (P = 0.002) and showed a close correlation (r = 0.76; P < 0.001). Treatment with a hydroxamic acid-type MMP inhibitor (GM6001; 65 mg/kg intraperitoneally every 12 h) beginning at the time of infection significantly lowered the MMP-9 (P< 0.02) and TNF-α (P < 0.02) levels in CSF. Histopathology at 25.5 ± 5.7 h after infection showed neuronal injury (median [range], 3.5% [0 to 17.5%] of the cortex), which was significantly (P < 0.01) reduced to 0% (0 to 10.8%) by GM6001. This is the first report to demonstrate that MMPs contribute to the development of neuronal injury in bacterial meningitis and that inhibition of MMPs may be an effective approach to prevent brain damage as a consequence of the disease.

scholarly journals Functional, inflammatory and interstitial impairment due to artificial stone dust ultrafine particles exposure

2019 ◽  
Vol 76 (12) ◽  
pp. 875-879 ◽  
Author(s):  
Noa Ophir ◽  
Amir Bar Shai ◽  
Rafi Korenstein ◽  
Mordechai R Kramer ◽  
Elizabeth Fireman
Keyword(s):  
Inflammatory Cytokines ◽  
Ultrafine Particles ◽  
Forced Expiratory Volume ◽  
Raw Material ◽  
High Dose ◽  
Necrosis Factor Alpha ◽  
Single Breath ◽  
Stone Dust ◽  
Tnf Α ◽  
Artificial Stone

ObjectiveArtificial stone dust (ASD) contains high levels of ultrafine particles (UFP <1 µm) which penetrate deeply into the lungs. This study aimed to demonstrate the direct effect of UFP in the lungs of ASD-exposed workers on functional inflammatory and imaging parameters.Methods68 workers with up to 20 years of ASD exposure at the workplace were recruited from small enterprises throughout the country and compared with 48 non-exposed individuals. Pulmonary function test (PFT), CT, induced sputum (IS) and cytokine analyses were performed by conventional methods. The CT scans were evaluated for features indicative of silicosis in three zones of each lung. UFP were quantitated by the NanoSight LM20 system (NanoSight, Salisbury) using the Nanoparticle Tracking Analysis. Interleukin (IL)-6, IL-8 and tumour necrosis factor alpha (TNF-α) levels were measured by Luminex (R&D Systems).ResultsThirty-four patients had CT scores between 0 and 42, and 29 of them were diagnosed with silicosis. Content of the UFP retrieved from IS supernatants correlated negatively with the PFT results (total lung capacity r=−0.347, p=0.011; forced expiratory volume in 1 s r=−0.299, p=0.046; diffusion lung carbon monoxide in a single breath r=−0.425, p=0.004) and with the CT score (r=0.378, p=0.023), and with the inflammatory cytokines IL-8 (r=0.336, p=0.024), IL-6 (r=0.294, p=0.065) and TNF-α (r=0.409, p=0.007). Raw material of ASD was left to sedimentate in water for <15 min, and 50% of the floating particles were UFP. A cut-off of 8×106 UFP/mL in IS samples had a sensitivity of 77% to predict pulmonary disease.ConclusionsThis is the first demonstration of an association between UFP-related decreased PFT results, worsening of CT findings and elevation of inflammatory cytokines, which may be attributed to high-dose inhalation of UFP of ASD at the workplace.

scholarly journals TNF-α interferes with lipid homeostasis and activates acute and proatherogenic processes

2007 ◽  
Vol 31 (2) ◽  
pp. 216-227 ◽  
Author(s):  
Klementina Fon Tacer ◽  
Drago Kuzman ◽  
Matej Seliškar ◽  
Denis Pompon ◽  
Damjana Rozman
Keyword(s):  
Regulatory Element ◽  
Hdl Cholesterol ◽  
Acid Synthesis ◽  
Farnesoid X Receptor ◽  
Lipid Homeostasis ◽  
Transcriptional Level ◽  
Necrosis Factor Alpha ◽  
Tnf Α ◽  
Element Binding Protein ◽  
Cytokine Tumor Necrosis Factor

The interaction between disrupted lipid homeostasis and immune response is implicated in the pathogenesis of several diseases, but the molecular bridges between the major players are still a matter of controversy. Our systemic study of the inflammatory cytokine tumor necrosis factor-alpha (TNF-α) in the livers of mice exposed to 20-h cytokine/fasting for the first time shows that TNF-α interferes with adaptation to fasting and activates harmful proatherogenic pathways, partially through interaction with the insulin-Insig-sterol regulatory element binding protein (Srebp) signaling pathway. In addition to the increased expression of acute-phase inflammatory genes, the most prominent alterations represent modified lipid homeostasis observed on the gene expression and metabolite levels. These include reduction of HDL-cholesterol, increase of LDL-cholesterol, and elevated expression of cholesterogenic genes, accompanied by increase of potentially harmful precholesterol metabolites and suppression of cholesterol elimination through bile acids, likely by farnesoid X receptor-independent mechanisms. On the transcriptional level, a shift from fatty oxidation toward fatty acid synthesis is observed. The concept of the influence of TNF-α on the Srebp regulatory network, followed by downstream effects on sterol metabolism, is novel. Observed acute alterations in lipid metabolism are in agreement with chronic disturbances found in patients.

scholarly journals Changes of Dry Eye Related Markers and Tear Inflammatory Cytokines After Upper Blepharoplasty

2021 ◽  
Vol 8 ◽  
Author(s):  
Songjiao Zhao ◽  
Nan Song ◽  
Lan Gong
Keyword(s):  
Inflammatory Cytokines ◽  
Dry Eye ◽  
Ocular Surface ◽  
Clinical Manifestations ◽  
Tear Film ◽  
Ocular Surface Disease Index ◽  
Necrosis Factor Alpha ◽  
Tnf Α ◽  
Break Up ◽  
Upper Blepharoplasty

Objectives: To investigate the changes of dry eye-related clinical manifestations, ocular surface parameters, and tear inflammatory cytokines after upper blepharoplasty.Methods: Forty eyes of 20 who underwent upper blepharoplasty were divided into either the group with or the group without preexisting dry eye before upper blepharoplasty. Ocular Surface Disease Index (OSDI), Schirmer I test, tear meniscus height, lipid layer thickness, non-invasive tear break-up time (NIKBUT), fluorescein tear film break-up time (FBUT), corneal fluorescein staining, meibum expression, lid margin changes, and tear inflammatory cytokines were assessed preoperatively and at 1, 3, and 6 months postoperatively. Correlations between inflammatory cytokines and dry eye-related parameters were determined.Results: The OSDI scores increased significantly at 1 month (p = 0.040) and subsequently decreased to the preoperative levels at 6 months postoperatively in subjects with dry eye. First (f)-NIKBUT and FBUT were significantly shortened at 1, 3, and 6 months postoperatively in subjects with dry eye (f-NIKBUT: p &lt;0.001, p = 0.010, p = 0.042; FBUT: p = 0.002, p = 0.005, p = 0.037, respectively), but were only shortened at 1 month (p = 0.028, p = 0.005) and returned to baseline levels at 6 months postoperatively in subjects without preexisting dry eye. A significant increasing trend of interleukin (IL)-6 was found in both dry eye and subjects without preexisting dry eye (p = 0.016, p = 0.008), while IL-8 and tumor necrosis factor alpha (TNF-α) were only found to be increased in subjects with dry eye postoperatively (p = 0.031, p = 0.031). The levels of IL-8 and TNF-α were positively correlated with OSDI scores (p = 0.046, p = 0.043, respectively) and negatively correlated with f-NIKBUT and FBUT (p = 0.026, p = 0.006, respectively).Conclusions: Upper blepharoplasty might increase the release of tear inflammatory cytokines and tear film instability that contribute to the development of postoperative dry eye in the early postoperative period and the changes most relieved in 6 months. Preexisting dry eye is a higher risk factor for worse and persistent ocular surface damage after upper blepharoplasty.

scholarly journals Impaired endothelial function irrespective of systemic inflammation or atherosclerosis in mastoscytosis

2020 ◽  
Author(s):  
Nida Oztop ◽  
Pelin Karaca Özer ◽  
semra demir ◽  
Sengul Beyaz ◽  
Tarık Tiryaki ◽  
...  
Keyword(s):  
Endothelial Dysfunction ◽  
Endothelial Function ◽  
Systemic Inflammation ◽  
Subclinical Atherosclerosis ◽  
Elevated Serum ◽  
Intima Media Thickness ◽  
Carotid Intima Media Thickness ◽  
Necrosis Factor Alpha ◽  
Endothelin 1 ◽  
Tnf Α

Background: Knowledge on endothelial dysfunction and its relation to atherosclerosis in mastocytosis is limited. Aim: To investigate the endothelial function in mastocytosis by flow mediated dilatation (FMD) and biomarkers related to vascular endothelia, the presence of subclinical atherosclerosis by carotid intima media thickness (CIMT). Method: Forty-nine patients with mastocytosis and 25 healthy controls (HCs) were included. FMD and CIMT during transthoracic echocardiography, biomarkers including endocan, endothelin-1 (ET-1), vascular endothelial growth factor (VEGF) were measured in sera of participants. Tumor necrosis factor-alpha (TNF-α), interleukine-6 (IL-6) and high sensitive c-reactive protein (hsCRP) were determined as inflammatory biomarkers. Result: The mean FMD% was lower in the patients than HCs (11.26±5.85% vs 17.84±5.27% p<0.001) and was the lowest in the advSM and SSM group among the patients (p=0.03). The median value of VEGF was significantly higher in patients than HCs. [73.30 pg/mL; min-max (32.46-295.29) pg/mL vs (46.64 pg/mL; min-max 11.09-99.86 pg/mL; p:0.001] and it was the highest in the advSM and SSM group (p:0.01). FMD was inversely correlated with endocan (r:-.390, p:0.006), ET-1 (r:-.363, p:0.01) and VEGF (r:-.402, p:0.004) but there were no correlations between FMD and TNF-α, IL-6, and hsCRP. No differences in CIMT values between patients and HCs and no correlation between CIMT and the biomarkers were observed. Conclusion: Endothelial dysfunction in mastocytosis becomes evident with decreased FMD and elevated serum VEGF, in the absence of atherosclerosis or systemic inflammation and is related to disease severity. Keywords: CIMT, Endocan, Endothelial function, Endothelin-1, FMD, VEGF

scholarly journals The Flavonoid Quercetin Inhibits Proinflammatory Cytokine (Tumor Necrosis Factor Alpha) Gene Expression in Normal Peripheral Blood Mononuclear Cells via Modulation of the NF-κβ System

2006 ◽  
Vol 13 (3) ◽  
pp. 319-328 ◽  
Author(s):  
Madhavan P. Nair ◽  
Supriya Mahajan ◽  
Jessica L. Reynolds ◽  
Ravikumar Aalinkeel ◽  
Harikrishnan Nair ◽  
...  
Keyword(s):  
Gene Expression ◽  
Proinflammatory Cytokine ◽  
Mononuclear Cells ◽  
Peripheral Blood Mononuclear ◽  
Necrosis Factor Alpha ◽  
Tnf Α ◽  
Cytokine Tumor Necrosis Factor ◽  
Factor Alpha ◽  
Anti Inflammatory ◽  
Necrosis Factor

ABSTRACT The flavonoids comprise a large class of low-molecular-weight plant metabolites ubiquitously distributed in food plants. These dietary antioxidants exert significant antitumor, antiallergic, and anti-inflammatory effects. The molecular mechanisms of their biological effects remain to be clearly understood. We investigated the anti-inflammatory potentials of a safe, common dietary flavonoid component, quercetin, for its ability to modulate the production and gene expression of the proinflammatory cytokine tumor necrosis factor alpha (TNF-α) by human peripheral blood mononuclear cells (PBMC). Our results showed that quercetin significantly inhibited TNF-α production and gene expression in a dose-dependent manner. Our results provide direct evidence of the anti-inflammatory effects of quercetin by PBMC, which are mediated by the inhibition of the proinflammatory cytokine TNF-α via modulation of NF-κβ1 and Iκβ.

scholarly journals Bile Mediates Intestinal Pathology in Endotoxemia in Rats

2000 ◽  
Vol 68 (8) ◽  
pp. 4714-4719 ◽  
Author(s):  
Graham D. F. Jackson ◽  
Yung Dai ◽  
William A. Sewell
Keyword(s):  
Endotoxic Shock ◽  
Intestinal Damage ◽  
External Drainage ◽  
Necrosis Factor Alpha ◽  
Intestinal Pathology ◽  
Tnf Α ◽  
Luminal Side ◽  
Factor Alpha ◽  
Duodenal Lumen ◽  
Necrosis Factor

ABSTRACT Intestinal pathology frequently accompanies experimental endotoxic shock and is mediated by proinflammatory cytokines. Our hypotheses are that hepatobiliary factors operating from the luminal side of the gut make a major contribution to this damage and that tumor necrosis factor alpha (TNF-α) is involved in the pathology. We treated rats with lipopolysaccharide (LPS) intravenously and found that external drainage of bile totally protected the gastrointestinal tract, macroscopically and microscopically, 4 h after LPS administration and dramatically improved survival of the animals for 48 h after LPS administration. The concentration of TNF-α in bile increased markedly after LPS administration and was over 30 times higher in bile than in serum. Tissue damage and the biliary TNF-α response were abrogated when animals were pretreated with gadolinium chloride to eliminate Kupffer cells. TNF-α infusion into the duodenal lumen caused intestinal damage similar to that elicited by intravenous LPS. In rats treated with LPS, survival was significantly increased during the first 36 h in animals given an infusion of anti-TNF-α antibody into the duodenum. These results demonstrate that in endotoxemia, intestinal damage is mediated by factors derived from the bile. The findings indicate that luminally acting TNF-α contributes to the intestinal damage.

Sign in / Sign up

Export Citation Format

Share Document