Dataset Information

Role of JAK-STAT Pathway in Broiler Chicks Fed with Chestnut Tannins.

ABSTRACT: The objective of this study was to identify the phosphorylation events associated with host immunity with the inclusion of chestnut tannins (ChT) in the diet. A total of 200 male day-of-hatch Cobb 500 chicks were randomly assigned to two treatment groups, totaling 50 chicks per pen per experiment (this study was repeated two times). The treatments were as follows: (1) control feed-normal starter feed (n = 50), and (2) 1% ChT inclusion feed (n = 50). The ceca were collected on each necropsy day for analysis via (1) a peptide array to provide tissue immunometabolism information from the host, and (2) quantitative PCR for mRNA expression. Of the top three immune pathways, the data identified the T-cell receptor signaling pathway, the chemokine signaling pathway, and the JAK-STAT signaling pathway. The results showed significantly altered phosphorylation of JAK and STAT peptides within the JAK-STAT pathway. These results support the mRNA expression data with the upregulated IL-6 response, due to the significant phosphorylation of IL6ST, JAK, and STAT peptides. In regard to immune modulation, ChT appear to influence host immunity via an IL-6 mediated response which could be beneficial in host defenses against pathogens at the early stages of broiler growth and development. Therefore, it is suggested that the role of the JAK-STAT pathway is altered by including ChT in the diet.

SUBMITTER: Lee A

PROVIDER: S-EPMC7911350 | biostudies-literature | 2021 Jan

REPOSITORIES: biostudies-literature

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Role of JAK-STAT Pathway in Broiler Chicks Fed with Chestnut Tannins.

Lee Annah A Cardoso Dal Pont Gabriela G Battaglia Michele M Arsenault Ryan J RJ Kogut Michael H MH

Animals : an open access journal from MDPI 20210129 2

The objective of this study was to identify the phosphorylation events associated with host immunity with the inclusion of chestnut tannins (ChT) in the diet. A total of 200 male day-of-hatch Cobb 500 chicks were randomly assigned to two treatment groups, totaling 50 chicks per pen per experiment (this study was repeated two times). The treatments were as follows: (1) control feed-normal starter feed (n = 50), and (2) 1% ChT inclusion feed (n = 50). The ceca were collected on each necropsy day f ...[more]

PMID: 33572892

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Project description:It is known that high doses of various tannins could impair broiler growth, and this seems to be linked to a lowered protein availability. However, effects on protein digestion under the influence of hydrolysable tannins were minimal in previous research and literature. Other possible proposed reasons to explain reduced growth are scarce. In this experiment we studied the effect of hydrolysable tannins on body allometry by using different feeding schemes throughout the rearing period. In total 112 individually reared male Ross 308 broilers received a 3-phase basal diet with chestnut wood extract (+: 2,000 mg/kg) or not (-: 0 mg/kg) (Tanno-SAN®, Sanluc International NV, Belgium). This resulted in 2 groups during the starter period (S+, S-), 4 groups in the grower period (G++, G+-, G-+, G-) and 8 groups in the finisher period (F+++, F++-, F+-+, F+--, F-++, F-+-, F--+, F--). Similar to previous studies, growth reduction was also observed in this study. Effects were the largest in broilers that were given the tannins during the grower phase. At the end of each phase 8 broilers per group were euthanized and sampled. Liver, pancreas, pectoralis muscle, intestinal weights and intestinal length were recorded. The largest effects were seen on the intestine. Broilers that received tannins during the grower phase, had longer intestines at the end of the finisher period. Furthermore, histological differences between treatment groups were observed at the end of the grower period. Addition of tannins in the grower phase (G-+, G++) resulted in longer villi, whereas addition of tannins in the starter (G+-, G++) caused deeper crypts at the end of the grower phase, with the group (G-+) having the highest villi-to-crypt ratio. These results tentatively prove that tannins influence intestinal growth, both macroscopically as well as histologically. We hypothesize that the observed growth reduction with tannins could be the result of a changed energy and nutrient partitioning, i.e., more nutrients are directed to intestinal growth than for muscle growth.

Project description:As the demand for alternatives to antibiotic growth promoters (AGP) increases in food animal production, phytobiotic compounds gain popularity because of their ability to mimic the desirable bioactive properties of AGP. Chestnut tannins (ChT) are one of many phytobiotic compounds used as feed additives, particularly in South America, for broilers because of its favorable antimicrobial and growth promotion capabilities. Although studies have observed the microbiological and immunologic effects of ChT, there is a lack of studies evaluating the metabolic function of ChT. Therefore, the objective of this study was to characterize the cecal metabolic changes induced by ChT inclusion and how they relate to growth promotion. A total of 200 day-of-hatch broiler chicks were separated into 2 feed treatment groups: control and 1% ChT. The ceca from all the chicks in the treatment groups were collected on day 2, 4, 6, 8, and 10 after hatch. The cytokine mRNA quantitative RT-PCR was determined using TaqMan gene expression assays for IL-1B, IL-6, IL-8, IL-10, and interferon gamma quantification. The cytokine expression showed highly significant increased expressions of IL-6 and IL-10 on day 2 and 6, whereas the other proinflammatory cytokines did not have significantly increased expression. The results from the kinome array demonstrated that the ceca from birds fed with 1% ChT had significant (P < 0.05) metabolic alterations based on the number of peptides when compared with the control group across all day tested. The increased expression of IL-6 appeared to be strongly indicative of altered metabolism, whereas the increased expression of IL-10 indicated the regulatory effect against other proinflammatory cytokines other than IL-6. The ChT initiate a metabolic mechanism during the first 10 d in the broiler. For the first time, we show that a phytobiotic product initially modulates metabolism while also potentially supporting growth and feed efficiency downstream. In conclusion, a metabolic phenotype alteration in the ceca of chickens fed ChT may indicate the importance of enhanced broiler gut health.

Project description:The goal of this study was to determine the role of the Janus tyrosine kinase (JAK)-signal transducers and activators of transcription (STAT) pathway in the late phase of ischemic preconditioning (PC). A total of 230 mice were used. At 5 min after ischemic PC (induced with six cycles of 4-min coronary occlusion/4-min reperfusion), immunoprecipitation with anti-phosphotyrosine (anti-pTyr) antibodies followed by immunoblotting with anti-JAK antibodies revealed increased tyrosine phosphorylation of JAK1 (+257 +/- 53%) and JAK2 (+238 +/- 35%), indicating rapid activation of these two kinases. Similar results were obtained by immunoblotting with anti-pTyr-JAK1 and anti-pTyr-JAK2 antibodies. Western analysis with anti-pTyr-STAT antibodies demonstrated a marked increase in nuclear pTyr-STAT1 (+301 +/- 61%) and pTyr-STAT3 (+253 +/- 60%) 30 min after ischemic PC, which was associated with redistribution of STAT1 and STAT3 from the cytosolic to the nuclear fraction and with an increase in STAT1 and STAT3 gamma-IFN activation site DNA-binding activity (+606 +/- 64%), indicating activation of STAT1 and STAT3. No nuclear translocation or tyrosine phosphorylation of STAT2, STAT4, STAT5A, STAT5B, or STAT6 was observed. Pretreatment with the JAK inhibitor AG-490 20 min before the six occlusion/reperfusion cycles blocked the enhanced tyrosine phosphorylation of JAK1 and JAK2 and the increased tyrosine phosphorylation, nuclear translocation, and enhanced DNA-binding activity of STAT1 and STAT3. The same dose of AG-490 abrogated the protection against myocardial infarction and the concomitant up-regulation of inducible NO synthase (iNOS) protein and activity observed 24 h after ischemic PC. Taken together, these results demonstrate that ischemic PC induces isoform-selective activation of JAK1, JAK2, STAT1, and STAT3, and that ablation of this response impedes the up-regulation of iNOS and the concurrent acquisition of ischemic tolerance. This study demonstrates that the JAK-STAT pathway plays an essential role in the development of late PC. The results reveal a signaling mechanism that underlies the transcriptional up-regulation of the cardiac iNOS gene and the adaptation of the heart to ischemic stress.

Project description:BackgroundThe JAK/STAT pathway transduces signals from multiple cytokines and controls haematopoiesis, immunity and inflammation. In addition, pathological activation is seen in multiple malignancies including the myeloproliferative neoplasms (MPNs). Given this, drug development efforts have targeted the pathway with JAK inhibitors such as ruxolitinib. Although effective, high costs and side effects have limited its adoption. Thus, a need for effective low cost treatments remains.Methods & findingsWe used the low-complexity Drosophila melanogaster pathway to screen for small molecules that modulate JAK/STAT signalling. This screen identified methotrexate and the closely related aminopterin as potent suppressors of STAT activation. We show that methotrexate suppresses human JAK/STAT signalling without affecting other phosphorylation-dependent pathways. Furthermore, methotrexate significantly reduces STAT5 phosphorylation in cells expressing JAK2 V617F, a mutation associated with most human MPNs. Methotrexate acts independently of dihydrofolate reductase (DHFR) and is comparable to the JAK1/2 inhibitor ruxolitinib. However, cells treated with methotrexate still retain their ability to respond to physiological levels of the ligand erythropoietin.ConclusionsAminopterin and methotrexate represent the first chemotherapy agents developed and act as competitive inhibitors of DHFR. Methotrexate is also widely used at low doses to treat inflammatory and immune-mediated conditions including rheumatoid arthritis. In this low-dose regime, folate supplements are given to mitigate side effects by bypassing the biochemical requirement for DHFR. Although independent of DHFR, the mechanism-of-action underlying the low-dose effects of methotrexate is unknown. Given that multiple pro-inflammatory cytokines signal through the pathway, we suggest that suppression of the JAK/STAT pathway is likely to be the principal anti-inflammatory and immunosuppressive mechanism-of-action of low-dose methotrexate. In addition, we suggest that patients with JAK/STAT-associated haematological malignancies may benefit from low-dose methotrexate treatments. While the JAK1/2 inhibitor ruxolitinib is effective, a £43,200 annual cost precludes widespread adoption. With an annual methotrexate cost of around £32, our findings represent an important development with significant future potential.

Project description:Antimicrobial restrictions prompted the search for cost and biologically effective alternatives to replace antimicrobial growth promoters (AGPs) in food-producing animals. In addition, the efficacy of this alternatives needs to be contrasted in field/commercial trials under different challenge conditions. However only a few studies describing the impact of tannins or others AGP-alternatives in commercial poultry production conditions are actually available. The aim of the present work is to study how the inclusion of a blend of chestnut and quebracho tannins can affect broiler productive performance and health under commercial conditions. Three experiments with different approaches were conducted: (1) a trial comparing the effects of both additives (tannins vs AGP) on different commercial farms at the same time; (2) the follow-up of one farm during an entire productive year; and (3) an experimental trial using a C. perfringens challenge model in broiler chickens. Although productive results from field trials were similar among treatments, evaluations of gut health indicators showed improvements in the tannins treated flocks. Frequency and severity of intestinal gross lesions were reduced in jejunum (42% vs 23%; p<0.05-1.37 vs. 0.73; p<0.01, respectively) and ileum (25% vs. 10%; p<0.0.5-1.05 vs. 0.58; p<0.01) in tannins treated birds. Results from 16S studies, show that cecal microbiota diversity was not differentially affected by AGPs or tannins, but changes in the relative abundance of certain taxa were described, including Lactobacillus and Bifidobacterium groups. Results from experimental C. perfringens necrotic enteritis showed that tannins treated birds had reduced incidence of gross lesions in jejunum (43.75 vs. 74.19%; p<0.01) and ileum (18.75% vs. 45.16%; p<0.05) compared with control. These results suggest that AGPs can be replaced by tannins feed additives, and contribute in the implementation of antimicrobial-free programs in broilers without affecting health or performance.

Dataset Information

Role of JAK-STAT Pathway in Broiler Chicks Fed with Chestnut Tannins.

Publications

Role of JAK-STAT Pathway in Broiler Chicks Fed with Chestnut Tannins.

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