scholarly journals The capacity of foodstuffs to induce innate immune activation of human monocytesin vitrois dependent on food content of stimulants of Toll-like receptors 2 and 4

2010 ◽  
Vol 105 (1) ◽  
pp. 15-23 ◽  
Author(s):  
Clett Erridge
Keyword(s):  
Human Subjects ◽  
Meat Products ◽  
Low Grade ◽  
293 Cells ◽  
Tnf Α ◽  
Protease Treatment ◽  
Food Content ◽  
Cooking Times ◽  
Inflammatory Signalling

The ingestion of fatty meals is associated with a transient, low-grade systemic inflammatory response in human subjects, involving the activation of circulating monocytes and the secretion of pro-inflammatory cytokines. However, it is not yet clear how different foodstuffs may promote inflammatory signalling. In a screen of forty filter-sterilised soluble extracts from common foodstuffs, seven were found to induce the secretion of TNF-α and IL-6 from human monocytesin vitro.To investigate what may differentiate inflammatory from non-inflammatory food extracts, stimulants of Toll-like receptor (TLR) 2 and TLR4 were quantified using human embryonic kidney-293 cells transfected with each TLR, and calibrated with defined bacterial lipopeptide (BLP) and lipopolysaccharide (LPS) standards. These assays revealed that while most foods contained undetectable levels of TLR2 or TLR4 stimulants, all TNF-α-inducing foods contained stimulants of either TLR2 (up to 1100 ng BLP-equivalent/g) or TLR4 (up to 2700 ng LPS-equivalent/g) in both the soluble and insoluble fractions. TLR stimulants were present mainly in meat products and processed foods, but were minimal or undetectable in fresh fruit and vegetables. The capacity of food extracts to induce TNF-α secretion in monocytes correlated with the content of both TLR2 (r0·837) and TLR4 stimulants (r0·748), and was completely abolished by specific inhibition of TLR2 and TLR4. LPS and BLP were found to be highly resistant to typical cooking times and temperatures, low pH and protease treatment. In conclusion, apparently unspoiled foodstuffs can contain large quantities of stimulants of TLR2 and TLR4, both of which may regulate their capacity to stimulate inflammatory signalling.

Artificial meat and the future of the meat industry

2017 ◽  
Vol 57 (11) ◽  
pp. 2216 ◽  
Author(s):  
Sarah P. F. Bonny ◽  
Graham E. Gardner ◽  
David W. Pethick ◽  
Jean-François Hocquette
Keyword(s):  
New Technologies ◽  
Meat Products ◽  
Farming Systems ◽  
Processed Meat ◽  
Low Grade ◽  
Meat Industry ◽  
Ground Meat ◽  
Market Place ◽  
The Future

The global population is estimated to plateau at 9 billion by the year 2050; however, projected food-production estimates would supply for only 8 billion people, using the ‘business as usual’ approach. In particular, the meat industry would need to increase production by ~50–73%. In response, there are several different options that have the potential to satisfy demand and increase production. Some of these options require advanced technologies and many may be considered as ‘artificial’ by different consumer groups. Within the meat industry itself, available technologies include selective breeding, agroecology systems, animal cloning and genetic modification. Alternatively, meat proteins can be replaced or substituted with proteins from plants, fungi, algae or insects. Finally, meat products could be produced using in vitro culturing and three-dimensional printing techniques. The protein produced by these techniques can be considered in the following three categories: modified livestock systems, synthetic meat systems, and meat substitutes. In the future, it is likely that meat substitutes will increase market share through competition with low-grade cuts of meat, sausages, ground meat and processed meat. However, synthetic meat systems and meat substitutes have significant barriers to commercialisation and widespread adoption that will affect their presence at least in the high-end premium sector in the market. To meet growing demands for protein, and in the face of growing competition from other sectors, the conventional meat industry must adopt new technologies and farming systems. These must be tailored to the challenges facing the industry and must effectively respond to consumer demands and the changing market place.

scholarly journals The effect of marine oil-derived n-3 fatty acids on transepithelial calcium transport in Caco-2 cell models of healthy and inflamed intestines

2007 ◽  
Vol 97 (2) ◽  
pp. 281-288 ◽  
Author(s):  
Jennifer Gilman ◽  
Kevin D. Cashman
Keyword(s):  
Fatty Acids ◽  
Crohn’S Disease ◽  
Crohn's Disease ◽  
Human Subjects ◽  
Healthy Human ◽  
Marine Oil ◽  
Ca Transport ◽  
Tnf Α

Marine oil-derived n-3 fatty acids have been shown to stimulate intestinal Ca absorption in animal studies, but the effects of such fatty acids on Ca absorption in human subjects are relatively unknown. In particular, n-3 fatty acids may be of therapeutic value for some Crohn's disease patients who experience Ca malabsorption. Therefore, the aim of the present study was to investigate the effect of 20 : 5n-3 and 22 : 6n-3 on transepithelial Ca transport across monolayers of healthy Caco-2 cells as well as of TNF-α-treated Caco-2 cells (an in vitro model of Crohn's disease). Caco-2 cells were seeded onto permeable filter supports and allowed to differentiate into monolayers, which were treated with 80 μm-20 : 5n-3, 80 μm-22 : 6n-3, or 40 μm-20 : 5n-3+40 μm-22 : 6n-3 for 6 or 8 d, with or without co-treatment with TNF-α (10 ng/ml) (n 11–15 monolayers per treatment). On day 16, transepithelial and transcellular transport of 45Ca and fluorescein transport (a marker of paracellular diffusion) were measured. Treatment of healthy and inflamed Caco-2 cells with 20 : 5n-3, 22 : 6n-3 and both fatty acids combined for 8 d significantly (P < 0·005–0·01) increased total transepithelial Ca transport compared with that in control, effects which were mediated by an enhanced rate of transcellular Ca transport. The effects of n-3 fatty acids on Ca absorption after 6 d were less clear-cut. In conclusion, the present in vitro findings highlight the need to investigate the effect of marine oil-based n-3 fatty acids on Ca absorption in vivo in studies of healthy human subjects as well as of Crohn's disease patients.

scholarly journals Ageing and production of the cytokines in Chernobyl clean-up workers from Latvia

2009 ◽  
Vol 63 (3) ◽  
pp. 87-92
Author(s):  
Nataļja Kurjāne ◽  
Rūta Brūvere ◽  
Natālija Gabruševa ◽  
Elvīra Hagina ◽  
Tija Zvagule ◽  
...  
Keyword(s):  
Peripheral Blood ◽  
Blood Donors ◽  
Age Groups ◽  
Control Group ◽  
Low Grade ◽  
Peripheral Blood Mononuclear ◽  
Age Related ◽  
Good Ability ◽  
Tnf Α

Ageing and production of the cytokines in Chernobyl clean-up workers from Latvia Chronic low-grade inflammation with subsequent impairment of immune system function promotes the development of age-related diseases, such as cancers, degenerative and infection diseases. It is not yet clear, if exposure to ionising radiation accelerates the aging process. The aim of the present work was to estimate the production of several cytokines by peripheral blood cells of Latvia's Chernobyl clean-up workers depending on age. ELISA was employed to determine the plasma level of sIL-1β and sIL-6 as well as level of IL-4 and TNF-α spontaneous and 24h and 96h after in vitro stimulation of peripheral blood mononuclear cell cultures by lipopolysaccharide (LPS) and phytohemagglutinin (PHA) mitogens were determined in 40 Chernobyl clean-up workers 17 years after their work in Chernobyl and in 42 blood-donors without a history of occupational radiation exposure. The ability of peripheral blood leukocytes (PBL) to produce interferons (IFNs) was determined in 73 Chernobyl clean-up workers 15 years after the work in Chernobyl and in age-matched 63 blood-donors. IFNs were tested in whole blood cultures by standard virus cytopathic inhibition micromethod after their in vitro induction by Newcastle disease virus, phytohemagglutinin or double-stranded RNA. Individuals were divided into three age groups: age < 40, age 40-49 and age > 50. The ability of PBL to produce IFN was significantly decreased in all Chernobyl clean-up worker age groups in comparison with blood-donors (control groups). The incidence of good ability to produce IFN gradually decreased with age in the control group, but increased with age in aged-matched Chernobyl clean-up workers groups. The production TNF-α and IL-4 by peripheral blood mononuclear cells as well as sIL-1β level in plasma showed no significant differences between all the examined age groups. The sIL-6 level was gradually increased with age in Chernobyl clean-up workers. Our results showed that the concentration of pro-inflammation cytokine sIL-6 in peripheral blood plasma, as well as the ability of PBL to produce IFNs, in Chernobyl clean-up workers from Latvia is age dependent.

scholarly journals MCPIP1 Enhances TNF-α-Mediated Apoptosis through Downregulation of the NF-κB/cFLIP Axis

Biology ◽  
2021 ◽  
Vol 10 (7) ◽  
pp. 655
Author(s):  
Fat-Moon Suk ◽  
Chi-Ching Chang ◽  
Pei-Chi Sun ◽  
Wei-Ting Ke ◽  
Chia-Chen Chung ◽  
...  
Keyword(s):  
Immunofluorescence Assay ◽  
Caspase Inhibitor ◽  
Recognition Sequence ◽  
Apoptotic Pathway ◽  
Monocyte Chemoattractant Protein 1 ◽  
Caspase 1 ◽  
Iκb Kinase ◽  
293 Cells ◽  
Tnf Α

Monocyte chemoattractant protein-1-induced protein 1 (MCPIP1) is rapidly produced under proinflammatory stimuli, thereby feeding back to downregulate excessive inflammation. In this study, we used the stable, inducible expressions of wild-type (WT) MCPIP1 and an MCPIP1-D141N mutant in T-REx-293 cells by means of a tetracycline on (Tet-on) system. We found that WT MCPIP1 but not MCPIP1-D141N mutant expression dramatically increased apoptosis, caspase-3, -7, -8, and -9 activation, and c-Jun N-terminal kinase (JNK) phosphorylation in TNF-α-treated cells. The pan-caspase inhibitor, z-VAD-fmk, and the caspase-1 inhibitor, z-YVAD-fmk, but not the JNK inhibitor, SP600125, significantly reversed apoptosis and caspase activation in TNF-α/MCPIP1-treated cells. Surprisingly, MCPIP1 itself was also cleaved, and the cleavage was suppressed by treatment with the pan-caspase inhibitor and caspase-1 inhibitor. Moreover, MCPIP1 was found to contain a caspase-1/-4 consensus recognition sequence located in residues 234~238. As expected, the WT MCPIP1 but not the MCPIP1-D141N mutant suppressed NF-κB activation, as evidenced by inhibition of IκB kinase (IKK) phosphorylation and IκB degradation using Western blotting, IKK activity using in vitro kinase activity, and NF-κB translocation to nuclei using an immunofluorescence assay. Interestingly, MCPIP1 also significantly inhibited importin α3 and importin α4 expressions, which are major nuclear transporter receptors for NF-κB. Inhibition of NF-κB activation further downregulated expression of the caspase-8 inhibitor, cFLIP. In summary, the results suggest that MCPIP1 could enhance the TNF-α-induced apoptotic pathway through decreasing NF-κB activation and cFLIP expression.

scholarly journals Photosynthetically Controlled Spirulina, but Not Solar Spirulina, Inhibits TNF-α Secretion: Potential Implications for COVID-19-Related Cytokine Storm Therapy

2021 ◽  
Vol 23 (1) ◽  
pp. 149-155
Author(s):  
Asaf Tzachor ◽  
Or Rozen ◽  
Soliman Khatib ◽  
Sophie Jensen ◽  
Dorit Avni
Keyword(s):  
Therapeutic Potential ◽  
Human Subjects ◽  
Arthrospira Platensis ◽  
In Vivo Studies ◽  
Cytokine Storm ◽  
Blue Green Algae ◽  
Tnf Α ◽  
Novel Coronavirus

AbstractAn array of infections, including the novel coronavirus (SARS-CoV-2), trigger macrophage activation syndrome (MAS) and subsequently hypercytokinemia, commonly referred to as a cytokine storm (CS). It is postulated that CS is mainly responsible for critical COVID-19 cases, including acute respiratory distress syndrome (ARDS). Recognizing the therapeutic potential of Spirulina blue-green algae (Arthrospira platensis), in this in vitro stimulation study, LPS-activated macrophages and monocytes were treated with aqueous extracts of Spirulina, cultivated in either natural or controlled light conditions. We report that an extract of photosynthetically controlled Spirulina (LED Spirulina), at a concentration of 0.1 µg/mL, decreases macrophage and monocyte-induced TNF-α secretion levels by over 70% and 40%, respectively. We propose prompt in vivo studies in animal models and human subjects to determine the putative effectiveness of a natural, algae-based treatment for viral CS and ARDS, and explore the potential of a novel anti-TNF-α therapy. Graphical abstract

scholarly journals Effects of blackcurrant-based juice on atherosclerosis-related biomarkers in cultured macrophages and in human subjects after consumption of a high-energy meal

2011 ◽  
Vol 108 (2) ◽  
pp. 234-244 ◽  
Author(s):  
Patricia Huebbe ◽  
Katrin Giller ◽  
Sonia de Pascual-Teresa ◽  
Anne Arkenau ◽  
Berit Adolphi ◽  
...  
Keyword(s):  
Ascorbic Acid ◽  
Human Subjects ◽  
Radical Scavenging ◽  
High Energy ◽  
Treatment Groups ◽  
Radical Scavenging Capacity ◽  
Scavenging Capacity ◽  
Tnf Α ◽  
Meal Consumption

Regular consumption of fruit and vegetables may be associated with decreased CVD risk. In the present study, we investigated the effects of blackcurrant (BC) juice, rich in polyphenols and ascorbic acid, on oxidative and inflammatory biomarkers in cultured macrophages in vitro and in human subjects with an atherosclerosis-prone phenotype (after consumption of a high-energy meal). In cultured macrophages (RAW264.7), BC treatment significantly inhibited lipopolysaccharide-induced inflammation as indicated by lower mRNA levels of TNF-α, IL-1β and inducible NO synthase (iNOS) and lower nuclear p65 levels indicating decreased NF-κB activity. iNOS protein levels were lower and haem oxygenase 1 levels higher in BC-treated cells when compared with untreated controls. Subjects given a high-energy meal had elevated serum glucose and insulin levels with no significant difference between the BC-based juice and placebo treatment groups. TAG following meal ingestion tended to be attenuated after the BC treatment. Plasma ascorbic acid and radical-scavenging capacity were decreased following placebo meal consumption; however, BC significantly elevated both parameters compared with baseline and placebo ingestion. Plasma oxidised LDL, α-tocopherol and paraoxonase activity were unchanged in both treatment groups. Furthermore, production of TNF-α and IL-1β was not significantly changed by BC meal consumption. The present results suggest potential antioxidative and anti-inflammatory properties of BC in vitro in cultured macrophages. Although the observations were not directly transferable to a postprandial in vivo situation, the present results show that BC juice consumption may improve postprandial antioxidant status as indicated by higher ascorbic acid levels and free radical-scavenging capacity in plasma.

The preclinical anti-angiogenic and pro-apoptotic activity of lenalidomide in urothelial carcinoma (UC).

2013 ◽  
Vol 31 (6_suppl) ◽  
pp. 294-294
Author(s):  
Weiguo Jian ◽  
Jonathan M. Levitt ◽  
Keith S. Chan ◽  
Seth P. Lerner ◽  
Guru Sonpavde
Keyword(s):  
Flow Cytometry ◽  
Cell Viability ◽  
Cell Line ◽  
Immune Modulation ◽  
Human Subjects ◽  
Low Grade ◽  
Angiogenic Activity ◽  
Apoptotic Activity

294 Background: Lenalidomide (Len) is an immunomodulatory drug (IMiD) approved for hematologic conditions and demonstrates immune modulation, anti-angiogenic activity and direct anti-tumor cytotoxicity. A rationale can be made to evaluate the preclinical activity of Len in UC. Methods: The in vitro anti-tumor activity of Len was evaluated in 4 human (5637, TCC-SUP, RT4, RT112) and 1 murine (MB49) cell line. Anti-proliferative activity activity (MTT assay), apoptosis (Annexin-FITC immunohistochemistry [IHC], flow cytometry) and cell viability by colony forming assay were measured. In vivo activity of daily oral Len 10 mg/kg or placebo orally for 5 days a week for up to 4 weeks was examined in syngeneic immunocompetent C57BL/6 mice bearing subcutaneous (SC) MB49-Luc25 tumors and RT4 subcutaneous xenografts. Tumors underwent immunohistochemistry (IHC) for microvessel density (CD31), apoptosis (cleaved caspase [cc]-3) and CD3+/CD20+ lymphocyte infiltration. Cereblon, a molecular target of Len was analyzed by IHC. Results: In vitro cultures for 3 days with daily repletion of Len showed significant pro-apoptotic activity (flow cytometry) at low micromolar concentrations attainable in human subjects (2.2 µM) against RT4 cells, a superficially invasive human UC cell line. Long-term cultures of RT4 cells for 2 weeks with daily repletion of Len significantly reduced cell viability and colony forming ability. Cereblon expression was numerically lower in sensitive RT4 cells compared to resistant 5637 cells (p=NS). In the immunocompetent model in vivo, Len did not decrease tumor size, or increase cc-3 and CD3+/CD20+ lymphocytes, but post-Len tumors exhibited decreased CD31 (p<0.05). In RT4 xenografts, Len significantly decreased the size of tumors and CD31, and increased cc-3 (all p<0.05). Cereblon expression increased in Len treated RT4 xenografts (p=0.024). Conclusions: Lenalidomide demonstrated selective preclinical activity against superficially invasive low grade human UC cells attributable to direct tumor cell apoptosis and anti-angiogenic activity. Clinical evaluation in patients with low grade or non-invasive UC and further study of cereblon as a predictive biomarker may be warranted.

scholarly journals Metformin and Vitamin D Modulate Inflammation and Autophagy during Adipose-Derived Stem Cell Differentiation

2021 ◽  
Vol 22 (13) ◽  
pp. 6686
Author(s):  
Sara Cruciani ◽  
Giuseppe Garroni ◽  
Renzo Pala ◽  
Maria Laura Cossu ◽  
Giorgio Carlo Ginesu ◽  
...  
Keyword(s):  
Vitamin D ◽  
Stem Cell ◽  
Adipogenic Differentiation ◽  
Stem Cell Differentiation ◽  
Low Grade ◽  
Mrna Levels ◽  
Tnf Α ◽  
Shock Proteins

Adipose-derived stem cells (ADSCs) came out from the regenerative medicine landscape for their ability to differentiate into several phenotypes, contributing to tissue regeneration both in vitro and in vivo. Dysregulation in stem cell recruitment and differentiation during adipogenesis is linked to a chronic low-grade inflammation and macrophage infiltration inside the adipose tissue, insulin resistance, cardiovascular disease and obesity. In the present paper we aimed to evaluate the role of metformin and vitamin D, alone or in combination, in modulating inflammation and autophagy in ADSCs during adipogenic commitment. ADSCs were cultured for 21 days in the presence of a specific adipogenic differentiation medium, together with metformin, or vitamin D, or both. We then analyzed the expression of FoxO1 and Heat Shock Proteins (HSP) and the secretion of proinflammatory cytokines IL-6 and TNF-α by ELISA. Autophagy was also assessed by specific Western blot analysis of ATG12, LC3B I, and LC3B II expression. Our results showed the ability of the conditioned media to modulate adipogenic differentiation, finely tuning the inflammatory response and autophagy. We observed a modulation in HSP mRNA levels, and a significant downregulation in cytokine secretion. Taken together, our findings suggest the possible application of these molecules in clinical practice to counteract uncontrolled lipogenesis and prevent obesity and obesity-related metabolic disorders.

Euglycemic hyperinsulinemia augments the cytokine and endocrine responses to endotoxin in humans

2002 ◽  
Vol 282 (6) ◽  
pp. E1276-E1285 ◽  
Author(s):  
Mattias Soop ◽  
Helen Duxbury ◽  
Anselm O Agwunobi ◽  
J. Martin Gibson ◽  
Stephen J. Hopkins ◽  
...  
Keyword(s):  
Stress Responses ◽  
Inflammatory Responses ◽  
Experimental Studies ◽  
In Vitro Studies ◽  
Human Model ◽  
Saline Control ◽  
Plasma Norepinephrine ◽  
Low Grade ◽  
Tnf Α

Type 2 diabetes is associated with biochemical evidence of low-grade inflammation, and experimental studies have suggested that both insulin and glucose affect inflammatory responses. To determine the effect of in vivo changes in glucose availability and plasma insulin concentrations in humans, we administered 20 U/kg Escherichia coli lipopolysaccharide (LPS) or saline (control) to 14 subjects during a euglycemic hyperinsulinemic clamp ( n = 6) or an infusion of sterile saline ( n = 8). Parallel in vitro studies on human whole blood were undertaken to determine whether there was a direct effect of glucose, insulin, and leptin on proinflammatory cytokine production. Infusion of glucose and insulin significantly amplified and/or prolonged the cardiovascular, plasma interleukin-6 (IL-6), tumor necrosis factor-α (TNF-α), and counterregulatory hormone responses to LPS, whereas the effects on fever, plasma norepinephrine concentrations, and oxygen consumption were unaffected. In vitro studies showed no modulation of LPS-stimulated IL-6 or TNF-α production by glucose, insulin, or leptin at physiologically relevant concentrations. Hyperinsulinemia indirectly enhances key components of the systemic inflammatory and stress responses in this human model of infection.

Adipose tissue hypoxia and low-grade inflammation: a possible mechanism for ethanol-related glucose intolerance?

2015 ◽  
Vol 113 (9) ◽  
pp. 1355-1364 ◽  
Author(s):  
Zhen He ◽  
Min Li ◽  
Dongmei Zheng ◽  
Qing Chen ◽  
Wenwen Liu ◽  
...  
Keyword(s):  
Adipose Tissue ◽  
Glucose Tolerance ◽  
Hypoxia Inducible Factor ◽  
Ethanol Consumption ◽  
Oral Glucose ◽  
Low Grade ◽  
Tnf Α ◽  
Low Grade Inflammation

The exact mechanism of ethanol's effects on glucose tolerance has not been well determined. The present study focuses for the first time on hypoxia and low-grade inflammation in adipose tissue (AT). In the in vivo experiments, twenty-four male Wistar rats were randomly allocated into control and ethanol feeding groups. Ethanol-treated rats received edible ethanol once a day at a total dosage of 5 g/kg per d, and the controls received distilled water. Ethanol volumes were adjusted every week. At the end of 8 weeks, we carried out an oral glucose tolerance test. Blood and AT were collected for measuring hypoxia-inducible factor-1α (HIF-1α), GLUT1, TNF-α, IL-6, leptin and vascular endothelial growth factor (VEGF). In the in vitro experiments, differentiated OP9 adipocytes were incubated with 100 mm of ethanol for 48 h; the media and cells were then collected for measuring HIF-1α, GLUT1, TNF-α and IL-6. The results showed that long-term ethanol consumption impaired glucose tolerance in rats. Ethanol consumption had little influence on body weight, but both epididymal and perirenal AT were markedly enlarged in the ethanol-treated rats as compared to the controls. Visceral adipose tissue (VAT) had accumulated, and the protein levels of HIF-1α and GLUT1, the indicators of hypoxia in rat epididymal AT and OP9 adipocytes, were elevated. Secondary to the AT hypoxia, the levels of inflammation-related adipokines, such as TNF-α, IL-6, leptin and VEGF, were increased. Based on these findings, we conclude that VAT hypoxia and low-grade inflammation might be a new mechanism in the treatment of ethanol-related diabetes.

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