CpG oligodeoxynucleotide promotes protective immunity in the enteric mucosa and suppresses enterotoxigenic E. coli in the weaning piglets

Cheng, Qing; Jiang, Zhenggu; Xu, Chenchao; Li, Huazhou; Cao, Ding; Yang, Zhaihan; Cao, Guangjun; Zhang, Linghua

doi:10.1016/j.intimp.2010.07.006

Cited by 10 publications

(6 citation statements)

References 51 publications

(51 reference statements)

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“…The mechanism by which Sup-CaNP reduced systemic immunity is still under investigation but include inhibiting STAT phosphorylation which prevents the differentiation of allergen-activated Th2 cells into IL-4 producers (30) by blocking the signal transduction cascade needed to maintain inflammatory and autoimmune conditions (30,33). In contrast, spleen cells from mice fed CpG-CaNP produced more IFNγ and IL-33 after re-stimulation, consistent with the amplification of Th1-biased immunity observed by other groups after parenteral CpG administration (52,53). Consistent with their ability to activate inflammatory cells, the magnitude of AD was significantly worsened by administration of CpG-CaNP.…”

Section: Activity Of Orally Delivered Sup Odnsupporting

confidence: 84%

“…30,33 In contrast, spleen cells from mice fed CpG-CaNPs produced more IFNγ and IL-33 after restimulation, consistent with the amplification of Th1-biased immunity observed by other groups after parenteral CpG administration. 51,52 Consistent with their ability to activate inflammatory cells, the magnitude of AD was significantly worsened by the administration of CpG-CaNPs. In contrast, the severity of disease in mice treated with Sup-CaNPs was significantly reduced while CaNP alone or containing control ODN had no effect on disease.…”

Section: Activity Of Orally Delivered Sup Odnsmentioning

confidence: 87%

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Use of nanoparticles to deliver immunomodulatory oligonucleotides

Klinman

Sato

Shimosato

2015

WIREs Nanomed Nanobiotechnol

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Synthetic oligonucleotides (ODN) containing unmethylated ‘CpG motifs’ stimulate the innate immune system to produce cytokines, chemokines and polyreactive antibodies. CpG ODN have shown promise as vaccine adjuvants and for the treatment of infectious diseases and cancer. The immunostimulatory activity of CpG ODN is inhibited by DNA containing “suppressive” motifs. ODN expressing suppressive motifs (Sup ODN) reduce ongoing immune reactions and show promise in the treatment of autoimmune and inflammatory diseases. This work reviews recent progress in the use of nanoparticles as carriers of CpG and Sup ODN to target their delivery to the GI tract and lungs.

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Section: Activity Of Orally Delivered Sup Odnsupporting

confidence: 84%

Section: Activity Of Orally Delivered Sup Odnsmentioning

confidence: 87%

Use of nanoparticles to deliver immunomodulatory oligonucleotides

Klinman

Sato

Shimosato

2015

WIREs Nanomed Nanobiotechnol

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“…Additionally, most of work has been concentrated on the regulation of oxidative stress involving weaning stress syndrome, ischemia or reperfusion, inflammation, and other diseases in animals (Valko et al, 2007, Schwerin et al, 2009Deng et al, 2010). The changes and the regulation of gut microbiota in weaned piglets have also been paid more attention (Castillo et al, 2006;Konstantinov et al, 2006;Cheng et al, 2010). However, the underlying relationship between oxidative stress and microbiota in weaned piglets is still unclear.…”

Section: Introductionmentioning

confidence: 99%

Regulation of N-acetyl cysteine on gut redox status and major microbiota in weaned piglets1

Yang

Zhu

et al. 2014

Journal of Animal Science

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This study was conducted to explore the regulation of N-acetyl cysteine (NAC) on gut redox status and proliferation of selected microbiota in weaned piglets. A total of 150 newborn piglets from 15 litters were randomly divided by litter to the control group (normally suckling), the weaning group (fed the basal diet), and the NAC group (basal + NAC diet) with 5 litters per group. Activities of total antioxidant capacity (T-AOC), glutathione peroxidase (GSH-Px), superoxide dismutase (SOD), and inhibition capacity of hydroxyl radical (IHR), and contents of malondialdehyde (MDA), H2O2, and NO in the ileum, colon, and cecum were analyzed to profile oxidative stress states. The real-time absolute quantitative PCR reaction was employed to quantify the amounts of total bacteria, Lactobacillus, Bifidobacterium, and Escherichia coli. The N-acetyl cysteine, as a universal antioxidant, was used to improve the redox status. Results showed that weaning stress resulted in the occurrence of gut oxidative stress and changes of gut microbiota (P < 0.05). Compared with the weaned piglets, the activities of ileal, colonic, and cecal T-AOC; ileal and colonic GSH-Px; cecal SOD; and colonic and cecal IHR were enhanced (P < 0.05), and the concentrations of ileal and cecal H2O2, ileal and colonic NO, and colonic MDA were reduced (P < 0.05) in the NAC-treated piglets. An increase (P < 0.05) in gut Lactobacillus and Bifidobacterium, accompanied with a decrease (P < 0.05) in Escherichia coli counts, was also observed in the NAC group. Bivariate correlation indicated that Lactobacillus and Bifidobacterium were positively correlated (P < 0.05) with the activities of T-AOC, GSH-Px, and SOD and inversely related (P < 0.05) to increased levels of H2O2, NO, OH, and MDA, and Escherichia coli showed a strong positive association (P < 0.05) with increased levels of free radicals and MDA and a negative association (P < 0.05) with the activities of antioxidant enzymes in intestines of weaned piglets. We concluded that NAC constructively regulated on the changes of the gut redox status and microbiota in piglets in response to weaning stress. The observed correlations implied that the NAC effects on the gut microbiota were confirmed, partly through an effect on oxidative stress in piglets, providing evidence that gut microbiota may be potentially improved by the modulation of the redox status by an antioxidant, which has relevance for gut health and function.

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“…According to the Chinese Pharmacopoeia, simulated gastric fluid (as follows: 1.64 mL diluted hydrochloric acid and 1 g pepsin were dissolved in 100 mL pure water) and simulated intestinal fluid (as follows: 1 g trypsin and 0.68 g KH 2 PO 4 were dissolved in 100 mL pure water, the pH was adjusted to 6.8 by 0.1 M NaOH) were prepared [36]. To determine the content of pGH1-Ssa1/ Sis1 protein in Pichia pastoris X33, 1 g pGH1-Ssa1/Sis1 Pichia pastori X33 was collected by centrifugation after adding to 100 mL simulated gastric fluid for 6 h [37], then added to 100 mL simulated intestinal fluid and the amount of pGH1-Ssa1/Sis1 protein was determined by ELISA every hour [38]. Briefly, samples after incubation with the simulated intestinal fluid were incubated with a 1:3000 dilution of pGH polyclonal antibody [33] overnight at 4 °C and incubated with HRP conjugated goat antirabbit IgG (CWBIO, China) at a dilution of 1:5000.…”

Section: Preparation Of Pichia Pastoris X33 With Partial Broken Wallmentioning

confidence: 99%

Co-expressing GroEL–GroES, Ssa1–Sis1 and Bip–PDI chaperones for enhanced intracellular production and partial-wall breaking improved stability of porcine growth hormone

Deng

et al. 2020

Microb Cell Fact

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Porcine growth hormone (pGH) is a class of peptide hormones secreted from the pituitary gland, which can significantly improve growth and feed utilization of pigs. However, it is unstable and volatile in vitro. It needs to be encapsulated in liposomes when feeding livestock, whose high cost greatly limits its application in pig industry. Therefore we attempted to express pGH as intracellular soluble protein in Pichia pastoris and feed these yeasts with partial wall-breaking for swine, which could release directly pGH in intestine tract in case of being degraded in intestinal tract with low cost. In order to improve the intracellular soluble expression of pGH protein in Pichia pastoris and stability in vitro, we optimized the pGH gene, and screened molecular chaperones from E. coli and Pichia pastoris respectively for co-expressing with pGH. In addition, we had also explored conditions of mechanical crushing and fermentation. The results showed that the expression of intracellular soluble pGH protein was significantly increased after gene optimized and co-expressed with Ssa1-Sis1 chaperone from Pichia pastoris. Meanwhile, the optimal conditions of partial wall-breaking and fermentation of Pichia pastoris were confirmed, the data showed that the intracellular expression of the optimized pGH protein coexpressed with Ssa1-Sis1 could reach 340 mg/L with optimal conditions of partial wall-breaking and fermentation. Animal experiments verified that the optimized pGH protein co-expression with Ssa1-Sis1 had the best promoting effects on the growth of piglets. Our study demonstrated that Ssa1-Sis1 could enhance the intracellular soluble expression of pGH protein in Pichia pastoris and that partial wall-breaking of yeast could prevent pGH from degradation in vitro, release targetedly in the intestine and play its biological function effectively. Our study could provide a new idea to cut the cost effectively, establishing a theoretical basis for the clinic application of unstable substances in vitro.

show abstract

CpG oligodeoxynucleotide promotes protective immunity in the enteric mucosa and suppresses enterotoxigenic E. coli in the weaning piglets

Cited by 10 publications

References 51 publications

Use of nanoparticles to deliver immunomodulatory oligonucleotides

Use of nanoparticles to deliver immunomodulatory oligonucleotides

Regulation of N-acetyl cysteine on gut redox status and major microbiota in weaned piglets1

Co-expressing GroEL–GroES, Ssa1–Sis1 and Bip–PDI chaperones for enhanced intracellular production and partial-wall breaking improved stability of porcine growth hormone

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