Phytic acid modulates the morphology, immunological response of cytokines and β-defensins in porcine intestine exposed to deoxynivalenol and fumonisin B1

2021 ◽  
pp. 1-10
Author(s):  
E.O. da Silva ◽  
J.P. Santos ◽  
A.T. Morey ◽  
L.M. Yamauchi ◽  
A.P.F.R. Loureiro Bracarense

Occurrence of mycotoxins in agricultural products represents a risk for human and animal health. Therefore, there is a requirement of strategies to mitigate their harmful impacts. This study investigated the effects of phytic acid (IP6) on the immunological response of pro-(interleukin (IL)-1β, IL-6, IL-8, IL-10, interferon (IFN)-γ, tumour necrosis factor (TNF)-α) and anti-inflammatory (IL-10) cytokines and β-defensins 1 (pBD-1) and 2 (pBD-2) in porcine jejunal explants exposed to deoxynivalenol (DON) and fumonisin B1 (FB1). The explants were exposed to the following treatments: control, DON (10 μM), DON plus IP6 2.5 mM or 5 mM, FB1 (70 μM), FB1 IP6 plus 2.5 or 5 mM. The expression levels of the cytokines were measured by RT-qPCR. The exposure to FB1 and DON induced intestinal lesions. The presence of 2.5 and 5 mM IP6 inhibited the morphological changes induced by the mycotoxins. The explants exposed to DON showed an increase in the expression of IL-1β and IL-8 and a decrease in the levels of IL-6, IFN-γ, IL-10 and pBD-2. IP6 (5 mM) decreased the expression of IL-8 and increased the expression in pBD-1 and 2 compared to DON alone. FB1 induced a significant decrease in the levels of most of the pro-inflammatory cytokines, IL-10 and pBD-1, and an increase in IL-1β expression. The addition of IP6 5 mM induced significant increase in TNF-α expression compared to FB1. Taken together, the results suggest IP6 modulates immunological changes induced by DON and FB1 on intestinal mucosa resulting in beneficial effects that contribute to intestinal homeostasis and health.

Toxins ◽  
2019 ◽  
Vol 11 (1) ◽  
pp. 18 ◽  
Author(s):  
Elisângela O. Da Silva ◽  
Juliana R. Gerez ◽  
Miriam S. N. Hohmann ◽  
Waldiceu A. Verri ◽  
Ana Paula F. R. L. Bracarense

The purpose of the present study was to investigate the effects of phytic acid (IP6) on morphological and immunohistochemical parameters and oxidative stress response in intestinal explants of pigs exposed to fumonisin B1 (FB1) and/or deoxynivalenol (DON). The jejunal explants were exposed to the following treatments: vehicle, IP6 5 mM, DON 10 µM, FB1 70 µM, DON 10 µM + FB1 70 µM, DON 10 µM + IP6 5 mM, FB1 70 µM + IP6 5 mM, and DON 10 µM + FB1 70 µM + IP6 5 mM. The decrease in villus height and goblet cell density was more evident in DON and DON + FB1 treatments. In addition, a significant increase in cell apoptosis and cell proliferation and a decrease in E-cadherin expression were observed in the same groups. DON and FB1 exposure increased cyclooxygenase-2 expression and decreased the cellular antioxidant capacity. An increase in lipid peroxidation was observed in DON- and FB1-treated groups. IP6 showed beneficial effects, such as a reduction in intestinal morphological changes, cell apoptosis, cell proliferation, and cyclooxygenase-2 expression, and an increase in E-cadherin expression when compared with DON, FB1 alone, or DON and FB1 in association. IP6 inhibited oxidative stress and increased the antioxidant capacity in the explants exposed to mycotoxins.


Molecules ◽  
2020 ◽  
Vol 25 (16) ◽  
pp. 3573
Author(s):  
Lian-Chun Li ◽  
Zheng-Hong Pan ◽  
De-Sheng Ning ◽  
Yu-Xia Fu

Simonsinol is a natural sesqui-neolignan firstly isolated from the bark of Illicium simonsii. In this study, the anti-inflammatory activity of simonsinol was investigated with a lipopolysaccharide (LPS)-stimulated murine macrophages RAW264.7 cells model. The results demonstrated that simonsinol could antagonize the effect of LPS on morphological changes of RAW264.7 cells, and decrease the production of nitric oxide (NO), tumor necrosis factor α (TNF-α), and interleukin 6 (IL-6) in LPS-stimulated RAW264.7 cells, as determined by Griess assay and enzyme-linked immunosorbent assay (ELISA). Furthermore, simonsinol could downregulate transcription of inducible nitric oxide synthase (iNOS), TNF-α, and IL-6 as measured by reverse transcription polymerase chain reaction (RT-PCR), and inhibit phosphorylation of the alpha inhibitor of NF-κB (IκBα) as assayed by Western blot. In conclusion, these data demonstrate that simonsinol could inhibit inflammation response in LPS-stimulated RAW264.7 cells through the inactivation of the nuclear transcription factor kappa-B (NF-κB) signaling pathway.


2001 ◽  
Vol 69 (5) ◽  
pp. 2847-2852 ◽  
Author(s):  
Julia Y. Lee ◽  
Kathleen E. Sullivan

ABSTRACT Lipopolysaccharide (LPS) is a very potent inducer of tumor necrosis factor alpha (TNF-α) expression from monocytes and macrophages. Another inflammatory cytokine, gamma interferon (IFN-γ), can potentiate the effects of LPS, but the mechanism is not thoroughly understood. Previous reports emphasized the ability of IFN-γ to upregulate CD14 expression (the receptor for LPS), and nearly all studies have utilized sequential stimulation with IFN-γ followed by LPS to exploit this phenomenon. This study demonstrates that IFN-γ can upregulate the effect of LPS at the level of transcription. Human monoblastic Mono-Mac-6 cells produced up to threefold-greater levels of TNF-α when simultaneously stimulated with LPS and IFN-γ compared to treatment with LPS alone. RNase protection studies showed a similar increase in RNA beginning as early as within 30 min. The synthesis of TNF-α mRNA in IFN-γ- and LPS-treated Mono-Mac-6 cells was also temporally prolonged even though the message turnover rate was identical to that seen in LPS stimulated cells. The modulatory effect of IFN-γ may be mediated by Jak2.


2018 ◽  
Vol 57 (6) ◽  
pp. 757-763 ◽  
Author(s):  
C Pagliari ◽  
L Kanashiro-Galo ◽  
A C C Jesus ◽  
M G Saldanha ◽  
M N Sotto

AbstractMucosal lesions of paracoccidioidomycosis (PCM) are frequently described and clinically important. Macrophages are classified as M1 or M2. M1 are proinflammatory and M2 are related to chronicity. Dectin-1 recognizes β-glucan and plays an important role against fungal cells. The objective was to verify the presence of M1, M2, and dectin-1 and a possible correlation with Th1/Th2 cytokines in mucosal PCM lesions. In sum, 33 biopsies of oral PCM were submitted to histological and immunohistochemistry analysis, and positive cells were quantified. Eleven biopsies were characterized by compact granulomas (G1), 12 with loose granulomas (G2), and 10 with both kind of granulomas (G3). pSTAT-1 was equally increased in the three groups. G1 was characterized by an increased number of CD163+ macrophages. G2 presented similar number of arginase 1, iNOS, and CD163 expressing cells. G3 presented an increased number of cells expressing arginase 1 and CD163 over iNOS. G1 and G3 presented high number of cells expressing interferon (IFN)-γ; interleukin (IL) 5 was increased in G2 and G3; the expression of IL10 was similar among the three groups, and the expression of tumor necrosis factor (TNF)-α was higher in G3. G1 correlates to Th1 cytokines and pSTAT-1 and G2 correlates to Th2 cytokines. G3 presents both kinds of cytokines. We could not associate the expression of arginase-1, CD163, iNOS, and dectin-1 with the pattern of cytokines or kind of granuloma.


2021 ◽  
Vol 12 ◽  
Author(s):  
Wei Zhao ◽  
Chuantao Peng ◽  
Hafiz Arbab Sakandar ◽  
Lai-Yu Kwok ◽  
Wenyi Zhang

Lactobacillus (L.) plantarum strains, belong to lactic acid bacteria group, are considered indispensable probiotics. Here, we performed meta-analysis to evaluate the regulatory effects of L. plantarum on the immunity during clinical trials. This meta-analysis was conducted by searching across four most common literature databases, namely, Cochrane Central Register of Controlled Trials, Web of Science, Embase, and PubMed. Clinical trial articles that met the inclusion and exclusion criteria were analyzed by Review Manager (version 5.3). p-value < 0.05 of the total effect was considered statistically significant. Finally, total of 677 references were retrieved, among which six references and 18 randomized controlled trials were included in the meta-analysis. The mean differences observed at 95% confidence interval: interleukin (IL)-4, −0.48 pg/mL (−0.79 to −0.17; p < 0.05); IL-10, 9.88 pg/mL (6.52 to 13.2; p < 0.05); tumor necrosis factor (TNF)-α, −2.34 pg/mL (−3.5 to −1.19; p < 0.05); interferon (IFN)-γ, −0.99 pg/mL (−1.56 to −0.41; p < 0.05). Therefore, meta-analysis results suggested that L. plantarum could promote host immunity by regulating pro-inflammatory and anti-inflammatory cytokines.


Blood ◽  
1998 ◽  
Vol 91 (9) ◽  
pp. 3112-3117 ◽  
Author(s):  
Claudia Rieser ◽  
Christine Papesh ◽  
Manfred Herold ◽  
Günther Böck ◽  
Reinhold Ramoner ◽  
...  

The endotoxin (lipopolysaccharide)-induced cytokine response is followed by a state of unresponsiveness to lipopolysaccharide (LPS) referred to as LPS tolerance or endotoxin desensitization. LPS tolerance, which can be experimentally induced in vitro and in vivo, is also known to occur in septic disease. Here, we evaluated whether dendritic cells (DC), the most potent antigen-presenting cells, are also subject to this phenomenon. Single doses of LPS added at the initiation of DC culture inhibited in a dose-dependent fashion the production of tumor necrosis factor-α (TNF-α), interleukin-10 (IL-10), and IL-12, but not the production of IL-8, in response to a second LPS challenge in day-5 DC. In addition, the LPS-induced expression of the CD83 maturation antigen was inhibited in these cells. Moreover, the endocytic activity of DC generated in the presence of LPS was dramatically reduced. DC desensitized with LPS were potent stimulators of T-cell proliferation but poor inducers of interferon-γ (IFN-γ) production in the allogeneic mixed leukocyte reaction. TNF-α and prostaglandin E2, two major products of LPS stimulation, could replace LPS for the induction of tolerance to LPS. Moreover, treatment of desensitized DC with TNF-α plus prostaglandin E2 fully restored CD83 expression and partially restored IL-12 production as well as the IFN-γ–inducing activity of DC in the mixed leukocyte reaction. Our data show that human DC are highly susceptible to the induction of LPS tolerance, which seems to be a state of differential deactivation in which some functions are impaired whereas others are retained. Tolerization at the level of the professional antigen-presenting cell by inflammatory mediators may play an important role in septic disease and in the origin of cancers associated with chronic inflammation.


Pteridines ◽  
1996 ◽  
Vol 7 (3) ◽  
pp. 72-76
Author(s):  
Tadashi Lizuka ◽  
Mitsuyo Sasaki ◽  
Hitomi Kamisako ◽  
Ko Oishi ◽  
Shigeru Uemura ◽  
...  

Summary In Kawasaki disease patients, increases in excretion of urinary neopterin coincided with fever and monocytosis in peripheral blood. We examined the products of neopterin, tumor necrosis factor-α (TNFα) and Interleukin-1 β (1L-1β) from healthy adult macrophages/monocytes (Mφ>/M), after stimulation with several activators to obtain some understanding of Kawasaki disease. Upon stimulation with either lipopolysaccharide (LPS) or polyinosinate-polycytidylate (Poly I:C), the Mφ/M released neopterin and pyogenic products (TNF-α or 1L-1β). The release of neopterin was eliminated by the addition of the anti-interferon-y antibody. The production of both TNF-α, 1L-1β and neopterin from Mφ/M upon stimulation of LPS was augmented in a co-culture with low dose recombinant interferon-y (rIFN-γ). Upon stimulation with rIFN-γ alone, however, the Mφ/M released neopterin but not the pyogenic products. A preliminary examination failed to detect. any difference in the response of the Mφ/M in adults annd children after stimulation with LPS. We concluded that some endotoxins could trigger the onset of Kawasaki disease and that endogenous IFN-γ can play an important role in the abnormality of Kawasaki disease patients


2020 ◽  
Vol 2020 ◽  
pp. 1-10
Author(s):  
Ruxing Zhao ◽  
Yujing Sun ◽  
Yongyuan Zhang ◽  
Weili Wang ◽  
Shouyu Wang ◽  
...  

Background. COVID-19 caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has threatened every civilian as a global pandemic. The immune system poses the critical interactive chain between the human body and the virus. Here, we make efforts to examine whether comorbidity with type 2 diabetes (T2D) affects the immunological response in COVID-19 patients. Methods. We conducted a retrospective pilot study investigating immunological characteristics of confirmed cases of COVID-19 with or without comorbid T2D. Two subcohorts of sex- and age-matched participants were eligible for data analysis, of which 33 participants were with T2D and the remaining 37 were nondiabetic (NDM). Cellular immunity was assessed by flow cytometric determination of surface markers including CD3, CD4, CD8, CD19, CD16, and CD56 in peripheral blood. Levels of C reactive protein, immunoglobulin (IgG, IgM, IgA, and IgE), and complements (C3, C4) were detected by rate nephelometry immunoassay. And Th1/Th2 cytokines (IL-2, IL-4, IL-6, IL-10, TNF-α, and IFN-γ) were detected by Cytometric Bead Array. Results. Neutrophil counts were found to be significantly higher in the T2D group than in the NDM group and had a significant relevance with clinical severity. Lymphocyte frequencies showed no significant differences in the two groups. However, the proportions and absolute counts of T, Tc, Th, and NK cells decreased in both groups to different degrees. An abnormal increase in neutrophil count and a decrease in lymphocyte subpopulations may represent risk factors of COVID-19 severity. The level of IgG, IgM, IgA, C3, and C4 showed no significant difference between the two groups, while the IgE levels were higher in the T2D group than in the NDM group ( p < 0.05 ). Th1 cytokines including IFN-γ, TNF-α, and IL-6, as well as CRP, appeared significantly higher in the T2D group. Conclusions. The COVID-19 patients comorbid with T2D demonstrated distinguishable immunological parameters, which represented clinical relevancies with the predisposed disease severity in T2D.


2005 ◽  
Vol 73 (2) ◽  
pp. 849-858 ◽  
Author(s):  
Simone Korten ◽  
Richard J. Anderson ◽  
Carolyn M. Hannan ◽  
Eric G. Sheu ◽  
Robert Sinden ◽  
...  

ABSTRACT Understanding the protective mechanism in the liver induced by recombinant vaccines against the pre-erythrocytic stages of malaria is important for vaccine development. Most studies in mice have focused on splenic and peripheral blood T cells and identified gamma interferon (IFN-γ)-producing CD8+ T cells as correlates of protection, which can be induced by prime-boost vaccination with recombinant poxviruses. Invariant natural killer T (Vα14iNKT) cells can also protect against liver stage malaria, when activated, and are abundant in the liver. Since poxviruses have nonspecific immunomodulating effects, which are incompletely understood, we investigated whether recombinant poxviruses affect the protective properties of hepatic Vα14iNKT cells and thus vaccine efficacy. We show that intradermal vaccination with recombinant poxviruses activated Vα14iNKT cells and NK cells in the livers of BALB/c mice while inducing IFN-γ- and tumor necrosis factor alpha (TNF-α)-producing pre-erythrocytic stage antigen-specific CD8+ T cells. Greater numbers of hepatic Vα14iNKT cells secreted interleukin-4 than IFN-γ. Vaccinated Vα14iNKT-cell-deficient mice had lower, but still protective levels of hepatic and splenic IFN-γ+ and TNF-α+ CD8+ T cells and better protection rates later after challenge with Plasmodium berghei sporozoites. Therefore, vaccine-activated hepatic Vα14iNKT cells help in generating specific T cells but are not required for protection induced by recombinant poxviruses. Furthermore, double-positive INF-γ+/TNF-α+ CD8+ T cells were enriched in protected livers, suggesting that cells expressing both of these cytokines may be most relevant for protection.


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