scholarly journals Patulin, Deoxynivalenol, Zearalenone and T-2 Toxin Affect Viability and Modulate Cytokine Secretion in J774A.1 Murine Macrophages

2016 ◽  
Vol 8 (2) ◽  
pp. 22 ◽  
Author(s):  
Jonathan H. Loftus ◽  
Gregor S. Kijanka ◽  
Richard O’Kennedy ◽  
Christine E. Loscher

<p>Mycotoxins are secondary fungal metabolites, which occur in food and feed. They have detrimental effects on the health of humans and animals, and they are known to cause immunosuppression. In this study the effect of patulin, deoxynivalenol (DON), zearalenone (ZEN) and T-2 toxin exposure on the viability and the secretion of key pro- and anti-inflammatory cytokines from the murine macrophage cell line, J774A.1, was investigated.  Exposure of macrophages to high doses of ZEN (100,000 pg/mL) and T-2 toxin (10,000 and 100,000 pg/mL) resulted in a significant decrease (P &lt; 0.05 and P &lt; 0.01) in cell viability. Exposure of macrophages to these mycotoxins resulted in a dose-dependent modulation of cytokine secretion. Specifically, exposure to low doses of patulin (0.001, 0.1 and 1 pg/mL) resulted in a statistically significant decrease in the secretion of the pro-inflammatory cytokines interleukin (IL) 6 (IL-6) and tumor necrosis factor alpha (TNF-α), following stimulation with lipopolysaccharide (LPS), a component of Gram-negative bacterial cell walls. Treatment with low doses of DON (0.001 pg/mL) and ZEN (0.001 and 0.01 pg/mL) significantly decreased (P &lt; 0.01) the secretion of the pro-inflammatory cytokine IL-12p40, while several doses of T-2 toxin (0.001, 0.01, 0.1, 1 and 100 pg/mL) caused a significant decrease the expression of IL-6. Each of the mycotoxins also significantly increased the production of the anti-inflammatory cytokine IL-10, both before and after LPS stimulation. This data provides further insight into the mechanisms by which mycotoxins modulate the host immune response to exert their immunosuppressive activity.</p>

2017 ◽  
Vol 2017 ◽  
pp. 1-8 ◽  
Author(s):  
Yang Huang ◽  
Zi Ye ◽  
Hang Li ◽  
Zhaohui Li

Purpose. To further investigate the pathogenesis of late-onset capsular block syndrome (CBS) and to evaluate the safety of surgical treatment.Methods. Seven patients diagnosed with late-onset CBS were retrospectively analyzed. Anterior chamber depth (ACD), intraocular pressure (IOP), refractive diopter, and best-corrected visual acuity (BCVA) before and after surgery were recorded. The opaque substance was tested with Western blot, and a flow cytometer multiple array assay system was utilized to evaluate the levels of inflammatory cytokines from opaque substance and aqueous humor, respectively.Results. Patients who had undergone surgical treatment showed a significant BCVA and spherical equivalent refractive error improvement (P=0.002,P=0.021, resp.). Nevertheless, ACD and IOP before and after surgery were in normal range with no difference (P=0.165,P=0.749, resp.).αB-crystallin andβB-crystallin were detected in all opaque substances. Tumor necrosis factor-alpha (TNF-α) and interlukin-1β(IL-1β) levels in opaque substance were significantly higher than those in aqueous humor (P=0.038,P=0.007, resp.), while IL-2 and IL-6 were not detected in any samples.Conclusions. Opaque substance is derived from human lens epithelial cells. Inflammatory cytokines may be involved in the pathogenesis of late-onset CBS. In addition, surgical treatment is an effective approach. This trial is registered withChiCTR-IOR-17011287.


2021 ◽  
Vol 99 (Supplement_3) ◽  
pp. 263-263
Author(s):  
Sergey Shabunin ◽  
Vitaly Mikhalev

Abstract The aim of the study was to research the cytokine profile of cow blood in the treatment of acute postpartum endometritis with the use of recombinant α-, γ-interferons. Animals of the first group (n = 9) with a diagnosis of acute postpartum endometritis were intramuscularly injected with propranolol hydrochloride, denatured emulsified placenta, and nioxityl. Propranolol hydrochloride was administered for 4 days at a dose of 10 ml/animal at 24-hour intervals. The denatured emulsified placenta was injected subcutaneously on days 1-5-9 at a dose of 25 ml /animal. Nioxityl was injected intrauterine at a dose of 150 ml three times with a 48-hour interval. Cows of the second group (n = 11) with the same diagnosis were additionally injected intramuscularly with bovine recombinant α-, γ-interferons three times in 1–3 days at a dose of 5 ml/animal, 1 cm3 of which contains at least 1x104 IU/cm3 of the total antiviral activity of bovine recombinant α-, γ-interferons. Blood samples are taken from all groups before and at the end of the experiment. Blood samples are examined for the content of interleukin-2 (IL-2), interleukin-4 (IL-4), tumor necrosis factor alpha (TNFα), interleukin-10 (IL-10) using Bovine Elisa Kit Clood-Clone Corp (USA). The therapeutic effectiveness in the first group was 77.8%, in the second - 90.9%, which is 13.1% more. At the end of the course, the level of IL-2 decreased by 42.5% (43.5±4.2 pg/ml, P &lt; 0.01), TNF-Α by 9.1% (457.9±34.6 pg/ml), the level of IL-4 increased by 14.8% (44.2±3.5 pg/ml, P &lt; 0.05), IL-10 by 56.6% (35.7±2.8 pg/ml, P &lt; 0.01). In the second group, the level of anti-inflammatory cytokines decreased: IL–2 by 48.7% (38.8±1.6 pg/ml, P &lt; 0.01), TNFα by 26% (372.5±17.6 pg/ml, P &lt; 0.05) and increased anti–inflammatory cytokines: IL-4 by 46.2% (56.3±4.1 pg/ml, P &lt; 0.001) and IL-10 by 80.3% (41.1±3.5 pg/ml, P &lt; 0.001), which indicates a decrease in the inflammatory response.


2010 ◽  
Vol 17 (5) ◽  
pp. 699-704 ◽  
Author(s):  
Sreedevi Srinivasan ◽  
Susan E. Leeman ◽  
Salomon Amar

ABSTRACT To begin to understand the surprising survival of macrophage-specific lipopolysaccharide-induced tumor necrosis factor alpha factor-deficient (macLITAF−/−) animals after a lethal dose of lipopolysaccharide (LPS), as reported earlier, the present follow-up study focuses on the role of LITAF in the regulation of inflammatory cytokines secreted in response to lethal or sublethal doses of LPS administered to wild-type (WT) and macLITAF−/− mice. A time course study of kinase expression in peritoneal macrophages revealed increased phosphorylation of prosurvival kinases Akt, Erk1/2, and ribosomal S6 kinase (RSK) in macLITAF−/− mice compared to that in WT mice (n = 8), confirming their role in LPS-mediated diseases. macLITAF−/− mice (n = 8) survived a lethal dose of LPS plus d-galactosamine (d-GalN), expressing lower serum levels of pro- and anti-inflammatory cytokines than the WT levels. To extend our knowledge on LPS-induced inflammatory events, an effective sublethal dose of LPS was administered to the animals (n = 14). WT animals exhibited an acute inflammatory response that decreased after 4 h. Interestingly, macLITAF−/− mice exhibited an initial delay in the secretion of proinflammatory cytokines that peaked after 8 h and reached WT levels after 18 h. Anti-inflammatory cytokine secretions were initially delayed but increased after 4 h and remained elevated compared to WT levels, even after 18 h. Our results demonstrate that LITAF deficiency in vivo affects cytokines other than TNF-α and influences the balance between the pro- and anti-inflammatory cytokines, which protects the animals from the deleterious effects of an LPS-induced inflammatory response, resulting in a beneficial host regulation of inflammatory cytokines and in enhanced survival. Therapeutic intervention aimed at reducing LITAF via kinase modulators may prove useful in preventing LPS-induced mortality.


2020 ◽  
Vol 90 (1-2) ◽  
pp. 103-112 ◽  
Author(s):  
Michael J. Haas ◽  
Marilu Jurado-Flores ◽  
Ramadan Hammoud ◽  
Victoria Feng ◽  
Krista Gonzales ◽  
...  

Abstract. Inflammatory and oxidative stress in endothelial cells are implicated in the pathogenesis of premature atherosclerosis in diabetes. To determine whether high-dextrose concentrations induce the expression of pro-inflammatory cytokines, human coronary artery endothelial cells (HCAEC) were exposed to either 5.5 or 27.5 mM dextrose for 24-hours and interleukin-1β (IL-1β), interleukin-2 (IL-2), interleukin-6 (IL-6), interleukin-8 (IL-8), and tumor necrosis factor α (TNF α) levels were measured by enzyme immunoassays. To determine the effect of antioxidants on inflammatory cytokine secretion, cells were also treated with α-tocopherol, ascorbic acid, and the glutathione peroxidase mimetic ebselen. Only the concentration of IL-1β in culture media from cells exposed to 27.5 mM dextrose increased relative to cells maintained in 5.5 mM dextrose. Treatment with α-tocopherol (10, 100, and 1,000 μM) and ascorbic acid (15, 150, and 1,500 μM) at the same time that the dextrose was added reduced IL-1β, IL-6, and IL-8 levels in culture media from cells maintained at 5.5 mM dextrose but had no effect on IL-1β, IL-6, and IL-8 levels in cells exposed to 27.5 mM dextrose. However, ebselen treatment reduced IL-1β, IL-6, and IL-8 levels in cells maintained in either 5.5 or 27.5 mM dextrose. IL-2 and TNF α concentrations in culture media were below the limit of detection under all experimental conditions studied suggesting that these cells may not synthesize detectable quantities of these cytokines. These results suggest that dextrose at certain concentrations may increase IL-1β levels and that antioxidants have differential effects on suppressing the secretion of pro-inflammatory cytokines in HCAEC.


2021 ◽  
Vol 22 (14) ◽  
pp. 7482
Author(s):  
Hwan Lee ◽  
Zhiming Liu ◽  
Chi-Su Yoon ◽  
Linsha Dong ◽  
Wonmin Ko ◽  
...  

Aging is associated with immune disregulation and oxidative stress which lead to inflammation and neurodegenerative diseases. We have tried to identify the anti-neuroinflammatory and anti-inflammatory components of Coreopsis lanceolata L. The dried flowers of C. lanceolata were extracted with 70% EtOH, and the obtained extract was divided into CH2Cl2, EtOAc, n-BuOH, and H2O fractions. The CH2Cl2 fraction was separated using silica gel and C-18 column chromatography to yield phenylheptatriyne (1), 2′-hydroxy-3,4,4′-trimethoxychalcone (2), and 4′,7-dimethoxyflavanone (3). Additionally, the EtOAc fraction was subjected to silica gel, C-18, and Sephadex LH-20 column chromatography to yield 8-methoxybutin (4) and leptosidin (5). All the compounds isolated from C. lanceolata inhibited the production of nitric oxide (NO) in LPS-induced BV2 and RAW264.7 cells. In addition, phenylheptatriyne and 4′,7-dimethoxyflavanone reduced the secretion of inflammatory cytokines, tumor necrosis factor alpha (TNF-α), and interleukin (IL)-6. Among them, phenylheptatriyne was significantly downregulated in the expression of inducible NO synthase (iNOS) and cyclooxygenase-2 (COX-2). Subsequently, phenylheptatriyne also effectively inhibited nuclear factor-kappa B (NF-κB) activation in LPS-stimulated BV2 and RAW264.7 cells. Based on these results, the anti-neuroinflammatory effect of phenylheptatriyne isolated from C. lanceolata was confirmed, which may exert a therapeutic effect in treatment of neuroinflammation-related diseases.


Pharmaceutics ◽  
2021 ◽  
Vol 13 (7) ◽  
pp. 956
Author(s):  
Yonelian Yuyun ◽  
Pahweenvaj Ratnatilaka Na Bhuket ◽  
Wiwat Supasena ◽  
Piyapan Suwattananuruk ◽  
Kemika Praengam ◽  
...  

Curcumin (CUR) has been used as adjuvant therapy for therapeutic application in the treatment of psoriasis through several mechanisms of action. Due to the poor oral bioavailability of CUR, several approaches have been developed to overcome the limitations of CUR, including the prodrug strategy. In this study, CUR was esterified with mycophenolic acid (MPA) as a novel conjugate prodrug. The MPA-CUR conjugate was structurally elucidated using FT-IR, 1H-NMR, 13C-NMR, and MS techniques. Bioavailable fractions (BFs) across Caco-2 cells of CUR, MPA, and MPA-CUR were collected for further biological activity evaluation representing an in vitro cellular transport model for oral administration. The antipsoriatic effect of the BFs was determined using antiproliferation and anti-inflammation assays against hyperproliferation of tumor necrosis factor-alpha (TNF-α)-induced human keratinocytes (HaCaT). The BF of MPA-CUR provided better antiproliferation than that of CUR (p < 0.001). The enhanced hyperproliferation suppression of the BF of MPA-CUR resulted from the reduction of several inflammatory cytokines, including IL-6, IL-8, and IL-1β. The molecular mechanisms of anti-inflammatory activity were mediated by an attenuated signaling cascade of MAPKs protein, i.e., p38, ERK, and JNK. Our results present evidence for the MPA-CUR conjugate as a promising therapeutic agent for treating psoriasis by antiproliferative and anti-inflammatory actions.


Pharmaceutics ◽  
2019 ◽  
Vol 11 (3) ◽  
pp. 143 ◽  
Author(s):  
Jingnan Zhao

Gold nanocages (AuNCs) are biocompatible and porous nanogold particles that have been widely used in biomedical fields. In this study, hyaluronic acid (HA) and peptide- modified gold nanocages (HA-AuNCs/T/P) loaded with 2-[(aminocarbonyl)amino]-5-(4-fluorophenyl)-3-thiophenecarboxamide (TPCA-1) were prepared to investigate their potential for combating inflammation. TPCA-1 was released from AuNCs, intracellularly when HA was hydrolyzed by hyaluronidase. HA-AuNCs/T/P show a much higher intracellular uptake than AuNCs/T/P, and exhibit a much higher efficacy on the suppression of tumor necrosis factor alpha (TNF-α) and interleukin 6 (IL-6) than free TPCA-1, suggesting great improvement to the anti-inflammatory efficacy of TPCA-1 through the application of AuNCs. HA-AuNCs/T/P can also reduce the production of reactive oxygen species in inflammatory cells. This study suggests that HA-AuNCs/T/P may be potential agents for anti-inflammatory treatment, and are worthy of further investigation.


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