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Glässer's disease, caused by Haemophilus parasuis, is a chronic disease related to an inflammatory immune response. Baicalin exerts important biological functions. In this study, we explored the protective efficacy of treatment with baicalin and the potential mechanism of activation of the MAPK signaling pathway in porcine aortic vascular endothelial cells (PAVECs) induced by H. parasuis. H. parasuis stimulated expression of receptor for advanced glycation end products, induced a significant increase in the level of protein kinase-α and protein kinase-δ phosphorylation, and significantly up-regulated ERK, c-Jun N-terminal kinase, and p38 phosphorylation in PAVECs. H. parasuis also up-regulated the levels of apoptotic genes (Bax, C-myc, and Fasl) and the expression levels of c-Jun and c-Fos, and induced S-phase arrest in PAVECs. However, treatment with baicalin inhibited expression of RAGE, suppressed H. parasuis -induced protein kinase-α and protein kinase-δ phosphorylation, reduced ERK, c-Jun N-terminal kinase, and p38 phosphorylation, down-regulated apoptotic genes (Bax, C-myc, and Fasl), attenuated phospho-c-Jun production from the extracellular to the nuclei, and reversed S-phase arrest in PAVECs. In conclusion, baicalin treatment inhibited the MAPK signaling pathway, thereby achieving its anti-inflammatory responses, which provides a new strategy to control H. parasuis infection. [ABSTRACT FROM AUTHOR]

Here, the potential mechanisms of the protective effects of fish oil against LPS-induced liver injury in a piglet model were investigated by using RNA sequencing. Twenty-four piglets were used in a 2 × 2 factorial design, and the main factors included diet (5% corn oil or 5% fish oil) and immunological challenge (LPS or saline, on d 19). All piglets were slaughtered at 4 h after challenge, and liver samples were collected. Fish oil improved liver morphology and reduced TNF-α, IL-1β and IL-6 productions after LPS challenge. RNA sequencing analysis showed fish oil had significant effect on the expressions of genes involved in immune response during LPS-induced inflammation. Selected gene expression changes were validated using quantitative RT-PCR. Fish oil reduced the expressions of pro-inflammatory genes IL1R1, IL1RAP, CEBPB and CRP, and increased that of anti-inflammatory genes IL-18BP, NFKBIA, IFIT1, IFIT2 and ATF3. Moreover, fish oil restored the expressions of some lipid metabolism-related genes, such as ACAA1, ACACA, ACADS and ACADM, which were only decreased in pigs fed a corn oil diet after LPS challenge. Our RNA sequencing reveals novel gene-nutrient interactions following fish oil supplementation and evoked inflammation, which add to the current understanding of the benefits of n-3 polyunsaturated fatty acids against liver injury. [ABSTRACT FROM AUTHOR]

Stress causes intestinal inflammation and barrier dysfunction. Corticotrophin-releasing factor (CRF)/CRF receptor (CRFR) signaling pathway has been shown to be important for stress-induced intestinal mucosal alteration. L-Asparagine (ASN) is a powerful stimulator of ornithine decarboxylase and cell proliferation in a variety of cell types, including colonic cells. In the present study, we investigated whether dietary ASN supplementation could alleviate the damage of intestinal barrier function caused by LPS through modulation of CRF/CRFR signaling pathway. Twenty-four weaned pigs were randomly divided into one of four treatments: (1) non-challenged control; (2) Escherichia coli LPS challenged control; (3) LPS + 0.5% ASN; (4) LPS + 1.0% ASN. LPS stress induced villous atrophy, intestinal morphology disruption and decreased claudin-1 expression. ASN supplementation increased intestinal claudin-1 protein expression and alleviated villous atrophy and intestinal morphology impairment caused by LPS stress. In addition, ASN supplementation increased the number of intestinal intraepithelial lymphocytes and reversed the elevations of intestinal mast cell number and neutrophil number induced by LPS stress. Moreover, ASN decreased the mRNA expression of intestinal CRF, glucocorticoid receptors and tryptase. These results indicate that ASN attenuates intestinal barrier dysfunction induced by LPS stress, and regulates CRF/CRFR1 signaling pathway and mast cell activation. [ABSTRACT FROM AUTHOR]

Infection and inflammation can result in the rapid loss of muscle mass and myofibrillar proteins (muscle atrophy). In addition, aspartate (Asp) is necessary for protein synthesis in mammalian cells. We hypothesized that Asp could attenuate LPS-induced muscle atrophy in a piglet model. Twenty-four weaning piglets were allotted to four treatments, including non-challenged control, LPS challenged control, LPS+0.5% Asp and LPS+1.0% Asp. On d 21, the piglets were injected with i.p. injection of LPS (100 ug/kg BM) or saline. At 4 h post-injection, blood, gastrocnemius and longissimus dorsi muscles samples were collected for biochemical and molecular analyses. Asp decreased the concentrations of cortisol and glucagon in plasma. In addition, Asp increased protein and RNA contents in muscles, and decreased mRNA expression of muscle atrophy F-box (MAFbx) and muscle RING finger 1 (MuRF1). Moreover, Asp decreased phosphorylation of AMPKα but increased phosphorylation of Akt and Forkhead Box O (FOXO) 1 in the muscles. Our results indicate that Asp suppresses LPS-induced MAFbx and MuRF1 expression via activation of Akt signaling, and inhibition of AMPKα and FOXO1 signaling. [ABSTRACT FROM AUTHOR]

In this study, the anti-inflammatory effects and mechanisms of baicalin on LPS-induced NLRP3 inflammatory pathway were investigated in piglet mononuclear phagocytes (control, LPS stimulation, LPS stimulation + 12.5 µg/ml baicalin, LPS stimulation + 25 µg/ml baicalin, LPS stimulation + 50 µg/ml baicalin and LPS stimulation + 100 µg/ml baicalin). The levels of reactive oxygen species (ROS), the secretion levels of IL-1β, IL-18 and TNF-α, mRNA expression levels of IL-1β, IL-18, TNF-α and NLRP3, as well as the protein levels of cleaved caspase-1 p20 were significantly increased after LPS-challenge in vitro. However, LPS stimulation did not influence apoptosis-associated speck-like protein and caspase-1 mRNA levels, which are also components of the NLRP3 inflammasome. Baicalin at 50 µg/ml and 100 µg/ml could inhibit the production of ROS, TNF-α, IL-1β and IL-18, and down-regulate mRNA expression of IL-1β, IL-18, TNF-α and NLRP3, as well as expression of cleaved caspase-1 p20. These results showed that the anti-inflammatory effects of baicalin occurred via the regulation of the release of ROS and mRNA expression of NLRP3. The anti-inflammatory activity of baicalin could be related to the suppression of NLRP3 inflammasome pathway under LPS stimulation. [ABSTRACT FROM AUTHOR]

This study evaluated whether fish oil exerted a hepatoprotective effect in a LPS-induced liver injury model via regulation of TLR4 and nucleotide-binding oligomerization domain protein (NOD) signaling pathways. Twenty-four piglets were used in a 2 × 2 factorial design, and the main factors included diet (5% corn oil or 5% fish oil) and immunological challenge (LPS or saline). Fish oil resulted in enrichment of eicosapentaenoic acid, docosahexaenoic acid and total (n-3) polyunsaturated fatty acids in liver. Less severe liver injury was observed in pigs fed fish oil, as evidenced by improved serum biochemical parameters and less severe histological liver damage. In addition, higher expression of liver tight junction proteins, and lower hepatocyte proliferation and higher hepatocyte apoptosis were observed in pigs fed fish oil. The improved liver integrity in pigs fed fish oil was concurrent with reduced hepatic mRNA expression of TLR4, myeloid differentiation factor 88, IL-1 receptor-associated kinase 1 and TNF-α receptor-associated factor 6, and NOD1, NOD2 and receptor-interacting serine/threonine-protein kinase 2, as well as reduced hepatic protein expression of NF-κB p65, leading to reduced hepatic pro-inflammatory mediators. These results indicate that fish oil improves liver integrity partially via inhibition of TLR4 and NOD signaling pathways under an inflammatory condition. [ABSTRACT FROM AUTHOR]

This study was conducted to evaluate whether dietary supplementation with L-arginine (Arg) could attenuate Escherichia coli LPS-induced liver injury through the TLR4 signaling pathway in weaned pigs. Eighteen weaned pigs were allotted to three treatments: non-challenged control, LPS challenged control and LPS + 0.5% Arg. On d 18, pigs were injected with LPS at 100 µg/kg of body weight (BW) or sterile saline. Blood samples were obtained at 4 h post-injection. Pigs were then sacrificed for the collection of liver samples. Arg supplementation (0.5%) alleviated liver morphological impairment, including hepatocyte caryolysis, karyopycnosis and fibroblast proliferation induced by LPS challenge; it mitigated the increase of serum aspartate aminotransferase and alkaline phosphatase activities induced by LPS (P < 0.05); it prevented the increase of hepatic TNF-α, malondialdehyde contents and mast cell number induced by LPS administration (P < 0.05); and it attenuated the elevation of hepatic NF-κB and TLR4-positive cell percentages (P < 0.05). These results indicate that Arg supplementation has beneficial effects in attenuating hepatic morphological and functional injury induced by LPS challenge in piglets. Additionally, it is possible that the protective effects of Arg on the liver are associated with a decreased release of liver pro-inflammatory cytokines and free radicals through inhibiting TLR4 signaling. [ABSTRACT FROM AUTHOR]