scholarly journals From Inflammation to the Onset of Fibrosis through A2A Receptors in Kidneys from Deceased Donors

2020 ◽  
Vol 21 (22) ◽  
pp. 8826
Author(s):  
Elena Guillén-Gómez ◽  
Irene Silva ◽  
Núria Serra ◽  
Francisco Caballero ◽  
Jesús Leal ◽  
...  
Keyword(s):  
Deceased Donor ◽  
Inflammatory Factors ◽  
Mrna Levels ◽  
A2a Adenosine Receptor ◽  
A2a Receptors ◽  
Tnf Α ◽  
Anti Inflammatory ◽  
Pka Pathway ◽  
Tgf Β1 ◽  
M2 Phenotype

Pretransplant graft inflammation could be involved in the worse prognosis of deceased donor (DD) kidney transplants. A2A adenosine receptor (A2AR) can stimulate anti-inflammatory M2 macrophages, leading to fibrosis if injury and inflammation persist. Pre-implantation biopsies of kidney donors (47 DD and 21 living donors (LD)) were used to analyze expression levels and activated intracellular pathways related to inflammatory and pro-fibrotic processes. A2AR expression and PKA pathway were enhanced in DD kidneys. A2AR gene expression correlated with TGF-β1 and other profibrotic markers, as well as CD163, C/EBPβ, and Col1A1, which are highly expressed in DD kidneys. TNF-α mRNA levels correlated with profibrotic and anti-inflammatory factors such as TGF-β1 and A2AR. Experiments with THP-1 cells point to the involvement of the TNF-α/NF-κB pathway in the up-regulation of A2AR, which induces the M2 phenotype increasing CD163 and TGF-β1 expression. In DD kidneys, the TNF-α/NF-κB pathway could be involved in the increase of A2AR expression, which would activate the PKA–CREB axis, inducing the macrophage M2 phenotype, TGF-β1 production, and ultimately, fibrosis. Thus, in inflamed DD kidneys, an increase in A2AR expression is associated with the onset of fibrosis, which may contribute to graft dysfunction and prognostic differences between DD and LD transplants.

scholarly journals Uremia impacts renal inflammatory cytokine gene expression in the setting of experimental acute kidney injury

2009 ◽  
Vol 297 (4) ◽  
pp. F961-F970 ◽  
Author(s):  
Richard A. Zager ◽  
Ali C. M. Johnson ◽  
Steve Lund
Keyword(s):  
Kidney Injury ◽  
Cytokine Gene Expression ◽  
Mrna Levels ◽  
Cytokine Gene ◽  
Cytokine Mrna ◽  
Pol Ii ◽  
Tnf Α ◽  
Anti Inflammatory ◽  
The Impact ◽  
Tgf Β1

Inflammatory cytokines are evoked by acute kidney injury (AKI) and may contribute to evolving renal disease. However, the impact of AKI-induced uremia on proinflammatory (e.g., TNF-α, MCP-1, TGF-β1) and anti-inflammatory (e.g., IL-10) cytokine gene expression remains unknown. This study was undertaken to gain some initial insights into this issue. CD-1 mice were subjected to left renal ischemia-reperfusion (I/R) in the absence or presence of uremia (± right ureteral transection). TNF-α, MCP-1, TGF-β1, and IL-10 mRNAs, cytokine protein levels, and RNA polymerase II (Pol II) recruitment to these genes were assessed. Renal cytokine mRNA levels were also contrasted with unilateral vs. bilateral renal parenchymal damage (I/R or ureteral obstruction). Potential effects of uremia on cytokine mRNAs in the absence of parenchymal renal damage [bilateral ureteral transection (BUTx)] were sought. Finally, the impact of simulated in vitro uremia (HK-2 tubular cells exposed to peritoneal dialysate from uremic vs. normal mice) on cytokine mRNA and microRNA profiles was assessed. Uremia blunted TNF-α, MCP-1, and TGF-β1 mRNA increases in all three in vivo parenchymal acute renal failure models. These results were paralleled by reductions in cytokine protein levels and Pol II recruitment to their respective genes. Conversely, uremia increased IL-10 mRNA, both in the presence and absence (BUTx) of parenchymal renal damage. The uremic milieu also suppressed HK-2 cell proinflammatory cytokine mRNA levels and altered the expression of least 69 microRNAs ( P < 0.0001). We conclude that both pro- and anti-inflammatory cytokine gene expressions are influenced by uremia, with a potential predilection toward an anti-inflammatory state. Changes in gene transcription (as reflected by Pol II recruitment), and possible posttranscriptional modifications (known to be induced by microRNAs), are likely involved.

scholarly journals Pirfenidone attenuates synovial fibrosis and postpones the progression of osteoarthritis by anti-fibrotic and anti-inflammatory properties in vivo and in vitro

2021 ◽  
Vol 19 (1) ◽  
Author(s):  
Qilu Wei ◽  
Ning Kong ◽  
Xiaohui Liu ◽  
Run Tian ◽  
Ming Jiao ◽  
...  
Keyword(s):  
Protein Expression ◽  
Cell Counting ◽  
Enzyme Linked Immunosorbent Assay ◽  
Fast Green ◽  
Expression Levels ◽  
Tnf Α ◽  
Anti Inflammatory ◽  
Safranin O ◽  
Tgf Β1

Abstract Background Osteoarthritis (OA) is a disease of the entire joint involving synovial fibrosis and inflammation. Pathological changes to the synovium can accelerate the progression of OA. Pirfenidone (PFD) is a potent anti-fibrotic drug with additional anti-inflammatory properties. However, the influence of PFD on OA is unknown. Methods Proliferation of human fibroblast-like synoviocytes (FLSs) after treatment with TGF-β1 or PFD was evaluated using a Cell Counting Kit-8 assay and their migration using a Transwell assay. The expression of fibrosis-related genes (COL1A1, TIMP-1, and ACTA-2) and those related to inflammation (IL-6 and TNF-α) was quantified by real-time quantitative PCR. The protein expression levels of COL1A1, α-SMA (coded by ACTA-2), IL-6 and TNF-α were measured by enzyme-linked immunosorbent assay. A rabbit model of OA was established and then PFD was administered by gavage. The expression of genes related to fibrosis (COL1A1, TIMP-1, and ADAM-12) and inflammation (IL-6 and TNF-α) was measured using RNA extracted from the synovium. Synovial tissue was examined histologically after staining with H&E, Masson’s trichrome, and immunofluorescence. Synovitis scores, the volume fraction of collagen, and mean fluorescence intensity were calculated. Degeneration of articular cartilage was analyzed using a Safranin O-fast green stain and OARSI grading. Results The proliferation of FLSs was greatest when induced with 2.5 ng/ml TGF-β1 although it did not promote their migration. Therefore, 2.5 ng/ml TGF-β1 was used to stimulate the FLSs and evaluate the effects of PFD, which inhibited the migration of FLSs at concentrations as low as 1.0 mg/ml. PFD decreased the expression of COL1A1 while TGF-β1 increased both mRNA and protein expression levels of IL-6 but had no effect on α-SMA or TNF-α expression. PFD decreased mRNA expression levels of COL1A1, IL-6, and TNF-α in vivo. H&E staining and synovitis scores indicated that PFD reduced synovial inflammation, while Masson’s trichrome and immunofluorescence staining suggested that PFD decreased synovial fibrosis. Safranin O-Fast Green staining and the OARSI scores demonstrated that PFD delayed the progression of OA. Conclusions PFD attenuated synovial fibrosis and inflammation, and postponed the progression of osteoarthritis in a modified Hulth model of OA in rabbits, which was related to its anti-fibrotic and anti-inflammatory properties.

scholarly journals Biomimetic nanotherapy: core–shell structured nanocomplexes based on the neutrophil membrane for targeted therapy of lymphoma

2021 ◽  
Vol 19 (1) ◽  
Author(s):  
Qiangqiang Zhao ◽  
Duanfeng Jiang ◽  
Xiaoying Sun ◽  
Qiuyu Mo ◽  
Shaobin Chen ◽  
...  
Keyword(s):  
Mesoporous Silica Nanoparticles ◽  
Treatment Options ◽  
Inflammatory Factors ◽  
Main Method ◽  
Tnf Α ◽  
Good Biocompatibility ◽  
Inflammatory Drugs ◽  
Anti Inflammatory ◽  
New Treatment ◽  
Lymphoma Therapy

Abstract Background Non-Hodgkin’s lymphoma (NHL) is a malignant disease of lymphoid tissue. At present, chemotherapy is still the main method for the treatment of NHL. R-CHOP can significantly improve the survival rate of patients. Unfortunately, DOX is the main cytotoxic drug in R-CHOP and it can lead to adverse reactions. Therefore, it is particularly important to uncover new treatment options for NHL. Results In this study, a novel anti-tumor nanoparticle complex Nm@MSNs-DOX/SM was designed and constructed in this study. Mesoporous silica nanoparticles (MSNs) loaded with Doxorubicin (DOX) and anti-inflammatory drugs Shanzhiside methylester (SM) were used as the core of nanoparticles. Neutrophil membrane (Nm) can be coated with multiple nanonuclei as a shell. DOX combined with SM can enhance the anti-tumor effect, and induce apoptosis of lymphoma cells and inhibit the expression of inflammatory factors related to tumorigenesis depending on the regulation of Bcl-2 family-mediated mitochondrial pathways, such as TNF-α and IL-1β. Consequently, the tumor microenvironment (TME) was reshaped, and the anti-tumor effect of DOX was amplified. Besides, Nm has good biocompatibility and can enhance the EPR effect of Nm@MSNs-DOX/SM and increase the effect of active targeting tumors. Conclusions This suggests that the Nm-modified drug delivery system Nm@MSNs-DOX/SM is a promising targeted chemotherapy and anti-inflammatory therapy nanocomplex, and may be employed as a specific and efficient anti-Lymphoma therapy.

Abstract 393: Anti-inflammatory Properties of Aqueous Extracts of Sesame Oil

2013 ◽  
Vol 33 (suppl_1) ◽  
Author(s):  
Krithika Selvarajan ◽  
Chandrakala Aluganti Narasimhulu ◽  
Reena Bapputty ◽  
Sampath Parthasarathy
Keyword(s):  
Protein Expression ◽  
Aqueous Extract ◽  
Dietary Intervention ◽  
Sesame Oil ◽  
Luciferase Assay ◽  
Treatment Modalities ◽  
Raw 264.7 Cells ◽  
Mrna Levels ◽  
Tnf Α ◽  
Anti Inflammatory

Background Dietary intervention to prevent atherosclerosis and inflammation has been a major focus in recent years. Sesame oil (SO), widely used in many Asian countries, has been reported to help reduce high blood pressure. It has also been shown to reduce plasma cholesterol, low density lipoprotein (LDL) cholesterol and triglyceride levels. We previously reported that SO was effective in inhibiting atherosclerosis in LDL-receptor negative mice. In this study we tested whether the aqueous, non-lipid components of SO might have anti-inflammatory effects. Methods Sesame oil was extracted using ethanol:water mixture, lyophilized and reconstituted in water. To study anti-inflammatory effect, RAW 264.7 cells (macrophage cell line) were treated with the aqueous extract in the presence or absence of lipopolysaccharide (LPS) for 24 hours. RNA was extracted using Trizol. mRNA expression of inflammatory cytokines such as IL-1α, IL-6 and TNF-α were analyzed by real time PCR. Protein expression was determined by western blot analysis. To identify the mechanism of action, we performed luciferase assay using HepG2-LXR reporter cell lines. Results LPS induced the expression of IL-1α, IL-6 and TNF-α mRNA levels in RAW cells. The extract alone did not significantly affect the expressions of inflammatory cytokine genes. However, when treated together with LPS, sesame oil aqueous extract inhibited the mRNA levels of these cytokines significantly. Treatment with LPS together with SO extract also decreased the protein expression of these cytokines. The SO extract induced LXR expression as identified by the luciferase assay system in HepG2-LXR reporter cells. Conclusion These findings suggest that the aqueous portion of SO might be effective in preventing inflammation. Furthermore, the activation of LXR might suggest additional effects on lipid metabolism. Identifying the specific components present in the aqueous extract will be instrumental in developing treatment modalities for atherosclerosis and other inflammatory conditions.

scholarly journals Pro- and Anti-Inflammatory Cytokines in the First Trimester—Comparison of Missed Miscarriage and Normal Pregnancy

2021 ◽  
Vol 18 (16) ◽  
pp. 8538
Author(s):  
Maciej Kwiatek ◽  
Tomasz Gęca ◽  
Anna Kwaśniewska
Keyword(s):  
Immune Response ◽  
Inflammatory Cytokines ◽  
First Trimester ◽  
Normal Pregnancy ◽  
Control Group ◽  
Study Group ◽  
Tnf Α ◽  
Cytokine Levels ◽  
Anti Inflammatory ◽  
Tgf Β1

The advantage in response of Th2 over Th1 is observed in normal pregnancy in peripheral blood. A disturbance of this balance can lead to symptoms of miscarriage and pregnancy loss. The aim of this study was to evaluate the pro- and anti-inflammatory cytokines in sera of women who were diagnosed with missed miscarriage in the first trimester and to compare this systemic immune response to the response in women with normal pregnancy. The study group consisted of 61 patients diagnosed with missed miscarriage. In total, 19 healthy women with uncomplicated first trimester created the control group. Cytokines were determined in the maternal serum by ELISA. The analysis included INF-γ, TNF-α, Il-1β, Il-4, Il-5, Il-6, Il-9, Il-10, Il-13 and TGF-β1. Th1 cytokine levels in the study group reached slightly higher values for INF-γ, Il-1β and slightly lower for IL-6 and TNF-α. In turn, Th2 cytokine levels in the study group were slightly higher (Il-9, Il-13), significantly higher (Il4, p = 0.015; Il-5, p = 0.0003) or showed no differences with the control group (Il-10). Slightly lower concentration involved only TGF-β1. Analysis of the correlation between levels of pro- and anti-inflammatory cytokines resulted in some discrepancies, without showing predominance of a specific immune response. The results did not confirm that women with missed miscarriage had an advantage in any type of immune response in comparison to women with normal pregnancy.

Oxymatrine inhibits lipopolysaccharide-induced inflammation by down-regulating Toll-like receptor 4/nuclear factor-kappa B in macrophages

2015 ◽  
Vol 93 (4) ◽  
pp. 253-260 ◽  
Author(s):  
Yu Zhang ◽  
Ruhong Yan ◽  
Yae Hu
Keyword(s):  
Nitric Oxide ◽  
Interleukin 1 ◽  
Chinese Herb ◽  
Mrna Levels ◽  
Nuclear Factor ◽  
Toll Like Receptor ◽  
Toll Like Receptor 4 ◽  
Necrosis Factor Alpha ◽  
Tnf Α ◽  
Anti Inflammatory

Oxymatrine (OMT) is the quinolizidine alkaloid extracted from the Chinese herb Sophora flavescens Ait. that has many pharmacological effects and is used for the treatment of some inflammatory diseases. In this study, RAW264.7 cells and THP-1 differentiated macrophages were pretreated with various concentrations of OMT at 2 h prior to treatment with lipopolysaccharide (LPS) (1.0 μg/mL) for different durations. We detected the anti-inflammatory effect of OMT in LPS-stimulated macrophages and investigated the molecular mechanism. We showed that OMT pretreatment significantly inhibited the LPS-induced secretion of nitric oxide (NO), interleukin-1 beta (IL-1β), and tumor necrosis factor-alpha (TNF-α) in supernatant, attenuated the mRNA levels of inducible nitric oxide synthase (iNOS), IL-1β, TNF-α, and Toll-like receptor 4 (TLR4), increased TLR4 and phosphorylation of inhibitor of kappa B-alpha (p-IBα) in cytosol, and decreased the nuclear level of nuclear factor-κB (NF-κB) p65 in macrophages. In conclusion, OMT exerts anti-inflammatory properties in LPS-stimulated macrophages by down-regulating the TLR4/NF-κB pathway.

Apoptosis perturbations and expression of regulatory inflammatory factors in cisplatin-depleted rat livers under l-arginine protection

2019 ◽  
Vol 97 (5) ◽  
pp. 359-369 ◽  
Author(s):  
Rehab M. El-Sayed ◽  
Hebatalla I. Ahmed ◽  
Abd El-Lateef S. Abd El-Lateef ◽  
Azza A. Ali
Keyword(s):  
Liver Function ◽  
Hepatic Injury ◽  
Inflammatory Factors ◽  
Protective Effects ◽  
Tnf Α ◽  
Apoptotic Marker ◽  
Apoptosis Markers ◽  
Anti Inflammatory ◽  
Rat Livers ◽  
Inflammatory Effect

Hepatic injury is one of the most common complications associated with cisplatin (CIS) use. Recently, liver protection lines are being discovered to stop the hepatic cell death due to inflammatory and apoptotic perturbations. l-arginine has protective effects in several models of liver injury. This study was designed to investigate the possible protective effect of l-arginine against CIS-induced acute hepatic injury in rats. Rats were divided into 4 groups: control, l-arginine, CIS, l-arginine + CIS. Liver function, oxidative stress, inflammatory cytokines, and apoptosis markers were assessed. l-arginine pretreatment protected the liver against CIS-induced toxicity as indicated by significantly alleviating the changes in liver function along with restoration of the antioxidant status. This finding was confirmed with the markedly improved pathological changes. l-arginine showed anti-inflammatory effect through the reduction of liver expression of iNOS, TNF-α, and NF-κβ, which were ameliorated to significant levels. Furthermore, l-arginine administration downregulated the liver expression of the apoptotic marker, caspase-3. The results recommend l-arginine as a hepatoprotective agent against CIS toxicity. Mostly, this hepatoprotective effect of l-arginine involved anti-inflammatory and anti-apoptotic activities.

scholarly journals Anti-Inflammatory Effects of Fucoxanthinol in LPS-Induced RAW264.7 Cells through the NAAA-PEA Pathway

Marine Drugs ◽  
2020 ◽  
Vol 18 (4) ◽  
pp. 222 ◽  
Author(s):  
Wenhui Jin ◽  
Longhe Yang ◽  
Zhiwei Yi ◽  
Hua Fang ◽  
Weizhu Chen ◽  
...  
Keyword(s):  
Nitric Oxide ◽  
Inhibitory Effect ◽  
Inflammatory Factors ◽  
Lipid Mediator ◽  
Peroxisome Proliferator ◽  
Necrosis Factor Alpha ◽  
Peroxisome Proliferator Activated Receptor ◽  
Tnf Α ◽  
Anti Inflammatory

Palmitoylethanolamide (PEA) is an endogenous lipid mediator with powerful anti-inflammatory and analgesic functions. PEA can be hydrolyzed by a lysosomal enzyme N-acylethanolamine acid amidase (NAAA), which is highly expressed in macrophages and other immune cells. The pharmacological inhibition of NAAA activity is a potential therapeutic strategy for inflammation-related diseases. Fucoxanthinol (FXOH) is a marine carotenoid from brown seaweeds with various beneficial effects. However, the anti-inflammatory effects and mechanism of action of FXOH in lipopolysaccharide (LPS)-stimulated macrophages remain unclear. This study aimed to explore the role of FXOH in the NAAA–PEA pathway and the anti-inflammatory effects based on this mechanism. In vitro results showed that FXOH can directly bind to the active site of NAAA protein and specifically inhibit the activity of NAAA enzyme. In an LPS-induced inflammatory model in macrophages, FXOH pretreatment significantly reversed the LPS-induced downregulation of PEA levels. FXOH also substantially attenuated the mRNA expression of inflammatory factors, including inducible nitric oxide synthase (iNOS), interleukin-6 (IL-6) and tumor necrosis factor-alpha (TNF-α), and markedly reduced the production of TNF-α, IL-6, IL-1β, and nitric oxide (NO). Moreover, the inhibitory effect of FXOH on NO induction was significantly abolished by the peroxisome proliferator-activated receptor α (PPAR-α) inhibitor GW6471. All these findings demonstrated that FXOH can prevent LPS-induced inflammation in macrophages, and its mechanisms may be associated with the regulation of the NAAA-PEA-PPAR-α pathway.

scholarly journals Daphnetin inhibits proliferation and inflammatory response in human HaCaT keratinocytes and ameliorates imiquimod-induced psoriasis-like skin lesion in mice

2020 ◽  
Vol 53 (1) ◽  
Author(s):  
Jintao Gao ◽  
Fangru Chen ◽  
Huanan Fang ◽  
Jing Mi ◽  
Qi Qi ◽  
...  
Keyword(s):  
Skin Lesion ◽  
Inflammatory Response ◽  
Mouse Model ◽  
Nuclear Translocation ◽  
Marker Gene ◽  
Inflammatory Factors ◽  
Mrna Levels ◽  
Hacat Keratinocytes ◽  
Tnf Α

Abstract Background Psoriasis is a common chronic inflammatory skin disease. Keratinocytes hyperproliferation and excessive inflammatory response contribute to psoriasis pathogenesis. The agents able to attenuate keratinocytes hyperproliferation and excessive inflammatory response are considered to be potentially useful for psoriasis treatment. Daphnetin exhibits broad bioactivities including anti-proliferation and anti-inflammatory. This study aims to evaluate the anti-psoriatic potential of daphnetin in vitro and in vivo, and explore underlying mechanisms. Methods HaCaT keratinocytes was stimulated with the mixture of IL-17A, IL-22, oncostatin M, IL-1α, and TNF-α (M5) to establish psoriatic keratinocyte model in vitro. Cell viability was measured using Cell Counting Kit-8 (CCK-8). Quantitative Real-Time PCR (qRT-PCR) was performed to measure the mRNA levels of hyperproliferative marker gene keratin 6 (KRT6), differentiation marker gene keratin 1 (KRT1) and inflammatory factors IL-1β, IL-6, IL-8, TNF-α, IL-23A and MCP-1. Western blotting was used to detect the protein levels of p65 and p-p65. Indirect immunofluorescence assay (IFA) was carried out to detect p65 nuclear translocation. Imiquimod (IMQ) was used to construct psoriasis-like mouse model. Psoriasis severity (erythema, scaling) was scored based on Psoriasis Area Severity Index (PASI). Hematoxylin and eosin (H&E) staining was performed to examine histological change in skin lesion. The expression of inflammatory factors including IL-6, TNF-α, IL-23A and IL-17A in skin lesion was measured by qRT-PCR. Results Daphnetin attenuated M5-induced hyperproliferation in HaCaT keratinocytes. M5 stimulation significantly upregulated mRNA levels of IL-1β, IL-6, IL-8, TNF-α, IL-23A and MCP-1. However, daphnetin treatment partially attenuated the upregulation of those inflammatory cytokines. Daphnetin was found to be able to inhibit p65 phosphorylation and nuclear translocation in HaCaT keratinocytes. In addition, daphnetin significantly ameliorate the severity of skin lesion (erythema, scaling and epidermal thickness, inflammatory cell infiltration) in IMQ-induced psoriasis-like mouse model. Daphnetin treatment attenuated IMQ-induced upregulation of inflammatory cytokines including IL-6, IL-23A and IL-17A in skin lesion of mice. Conclusions Daphnetin was able to attenuate proliferation and inflammatory response induced by M5 in HaCaT keratinocytes through suppression of NF-κB signaling pathway. Daphnetin could ameliorate the severity of skin lesion and improve inflammation status in IMQ-induced psoriasis-like mouse model. Daphnetin could be an attractive candidate for future development as an anti-psoriatic agent.

scholarly journals Nerolidol Mitigates Colonic Inflammation: An Experimental Study Using both In Vivo and In Vitro Models

Nutrients ◽  
2020 ◽  
Vol 12 (7) ◽  
pp. 2032
Author(s):  
Vishnu Raj ◽  
Balaji Venkataraman ◽  
Saeeda Almarzooqi ◽  
Sanjana Chandran ◽  
Shreesh K. Ojha ◽  
...  
Keyword(s):  
Nuclear Translocation ◽  
In Vitro Models ◽  
Mrna Levels ◽  
Colonic Inflammation ◽  
Tnf Α ◽  
Cox 2 ◽  
Anti Inflammatory ◽  
Ht 29

Nerolidol (NED) is a naturally occurring sesquiterpene alcohol present in various plants with potent anti-inflammatory effects. In the current study, we investigated NED as a putative anti-inflammatory compound in an experimental model of colonic inflammation. C57BL/6J male black mice (C57BL/6J) were administered 3% dextran sodium sulfate (DSS) in drinking water for 7 days to induce colitis. Six groups received either vehicle alone or DSS alone or DSS with oral NED (50, 100, and 150 mg/kg body weight/day by oral gavage) or DSS with sulfasalazine. Disease activity index (DAI), colonic histology, and biochemical parameters were measured. TNF-α-treated HT-29 cells were used as in vitro model of colonic inflammation to study NED (25 µM and 50 µM). NED significantly decreased the DAI and reduced the inflammation-associated changes in colon length as well as macroscopic and microscopic architecture of the colon. Changes in tissue Myeloperoxidase (MPO) concentrations, neutrophil and macrophage mRNA expression (CXCL2 and CCL2), and proinflammatory cytokine content (IL-1β, IL-6, and TNF-α) both at the protein and mRNA level were significantly reduced by NED. The increase in content of the proinflammatory enzymes, COX-2 and iNOS induced by DSS were also significantly inhibited by NED along with tissue nitrate levels. NED promoted Nrf2 nuclear translocation dose dependently. NED significantly increased antioxidant enzymes activity (Superoxide dismutase (SOD) and Catalase (CAT)), Hemeoxygenase-1 (HO-1), and SOD3 mRNA levels. NED treatment in TNF-α-challenged HT-29 cells significantly decreased proinflammatory chemokines (CXCL1, IL-8, CCL2) and COX-2 mRNA levels. NED supplementation attenuates colon inflammation through its potent antioxidant and anti-inflammatory activity both in in vivo and in vitro models of colonic inflammation.

Sign in / Sign up

Export Citation Format

Share Document