• Biomedical Science Letters
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• v.21 no.3
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• pp.152-159
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• 2015

Der p 2, which is a major allergen of house dust mite, plays an important role in the pathogenesis of allergic disease. There is controversy regarding whether Der p 2 binds to Toll-like receptor 4 (TLR4), and its inflammatory effect has not yet been elucidated. In the current study, we examined the interaction of Der p 2 with TLR4 and the effect of Der p 2 on cytokine release in THP-1 cells and lymphocytes. Among house dust mite extracts, recombinant TLR4 protein interacted with Der p 2. The overall structure of Der p 2 is characteristic of the immunoglobulin superfamily and contains ten ${\beta}-strands$, forming a ${\beta}-cup$ fold with two anti-parallel ${\beta}-sheets$, and a short 310 helix. The two sheets can be separated, further allowing the formation of a large internal pocket, which is narrow and suitable for binding large flat molecules such as lipid-like molecules. Der p 2 caused increased secretion of IL-6, IL-8, and MCP-1, which are neutrophil survival factors, in human monocytic THP-1 cells in a time-dependent manner. Der p 2 also induces the release of cytokines in normal and allergic lymphocytes. Supernatant after treatment with Der p 2 inhibited neutrophil apoptosis. In coculture of lymphocytes with neutrophils, Der p 2 inhibited spontaneous apoptosis of allergic neutrophils. In summary, Der p 2 binds to TLR4 and induces an inflammatory response such as cytokine secretion in immune cells. These findings may enable elucidation of allergy pathogenesis by specific allergen of house dust mite.

• Fisheries and Aquatic Sciences
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• v.21 no.6
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• pp.15.1-15.9
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• 2018

Background: Inflammation has been known to associate with many human diseases. The objective of this study was to evaluate an anti-inflammatory effect of ozonated krill (Euphausia superba) oil, which was prepared by the treatment of krill oil using ozone gas. The anti-inflammatory activity was evaluated in lipopolysaccharide (LPS)-stimulated RAW 264.7 macrophages. Results: Ozonated krill oil significantly inhibited nitric oxide (NO) production and suppressed the mRNA and protein expression of inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2) in LPS-stimulated RAW 264.7 macrophages. Ozonated krill oil also reduced the mRNA expression of inflammatory cytokines such as interleukin (IL)-$1{\beta}$, IL-6, and tumor necrosis factor (TNF)-${\alpha}$ in LPS-stimulated RAW 264.7 macrophages. To elucidate the mechanism underlying the anti-inflammatory activity of ozonated krill oil, we evaluated the effects of ozonated krill oil on the activation of mitogen-activated protein kinases (MAPKs) pathway. Ozonated krill oil suppressed the LPS-stimulated phosphorylation of p38 MAPK and c-Jun N-terminal kinases (JNK). Conclusion: This study revealed that the ozonated krill oil exhibited an anti-inflammatory effect in LPS-stimulated RAW 264.7 macrophages. To the best of our knowledge, this is the first report that ozonated krill oil suppressed pro-inflammatory mediator and cytokine expression in LPS-stimulated RAW 264.7 macrophages by inhibiting the phosphorylation of p38 MAPK and JNK.

• Journal of Physiology & Pathology in Korean Medicine
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• v.30 no.5
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• pp.338-346
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• 2016

Signal transducer and activator of transcription 3 (STAT3) is associated with various human diseases, such as cancer, auto-immune disease, and intestinal inflammation. The limited and inadequate effect of standard approaches for treating inflammatory bowel disease (IBD) has prompted to develop alternative anti-colitis agents through inhibition of STAT3. Here, we show that gallic acid (GA), a 3,4,5-trihydroxybenzoic acid, markedly reduced phosphorylation of STAT3. Among the derivatives of benzoic acids, GA showed significant inhibition on STAT3 phosphorylation. In addition, GA ameliorated the dextran sodium sulfate (DSS)-induced acute colitis as determined by the measurement of symptomatic and histological indices. The suppression of DSS-induced acute colitis by GA treatment may be related to the regulation of cytokines and growth factors. Furthermore, GA inhibited phosphorylation of STAT3 in the colon tissue of DSS-treated mice. These findings may be useful in comprehending the molecular action of GA on STAT3 phosphorylation and provide novel insights into the potential application of GA in the treatment of STAT3-related inflammatory disease, such as IBD.

• Journal of Physiology & Pathology in Korean Medicine
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• v.19 no.3
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• pp.779-784
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• 2005

Mast cells are a potent source of mediators that regulate the inflammatory response in allergic reaction. To evaluate the atopic allergic effect of Asiasari radix(AR), the author investigated a possible effect of AR on mast cell-mediated allergic reaction, cytokines secretion and mRNA expression in vivo and in vitro. In mice orally administered by AR (0.01, 0.1 and 1.0 g/kg) for 1 h, compound 48/80-induced ear swelling was significantly reduced (P < 0.05). AR had inhibitory effects on tumor necrosis factor $(TNF)-{\alpha}$, interleukin (IL)-8, and IL-6 secretion from HMC-1. Significant reduced levels of $TNF-{\alpha}$ mRNA was observed in the human mast cell line (HMC-1) with AR (1.0 mg/ml). In addition, AR had no cytotoxic effect on cell viability. These results suggest that AR contributes to the treatment of atopic allergic reactions, and that its action may be due to inhibition of cytokine secretion and mRNA expression in HMC-1.

• Journal of Physiology & Pathology in Korean Medicine
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• v.19 no.4
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• pp.934-937
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• 2005

Inflammatory cytokine, abundantly produced in Hashimoto's thyroiditis, induced Fas expression in normal thyrocytes. We determined that susceptibility to Fas-activated apoptosis could be influenced by inflammatory cytokine and investigated a potential role of Gamgung-tang (GGT, Glycyrrhizae Radix, black beans, Angelicae Radix and Cnidii Rhizoma) in the thyroid follicular cells. $IL-1\beta$ was able to induce Fas expression in normal thyrocytes. GGT inhibited $IL-1\beta-induced$ Fas expression. Thyroid follicular cells were found to undergo DNA fragmentation with the inflammatory cytokines. GGT inhibited DNA fragmentation in a dose-dependent manner. These results suggest that GGT inhibit Fas-mediated apoptosis in thyroid follicular cells, therefore, may have therapeutic potential in the treatment of autoimmune chronic thyroiditis.

• Biomolecules & Therapeutics
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• v.20 no.1
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• pp.36-42
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• 2012

Baicalin, a main constituent of the rhizome of Scutellaria baicalensis, is metabolized to baicalein and oroxylin A in the intestine before its absorption. To understand the role of intestinal microflora in the pharmacological activities of baicalin, we investigated its anti-inflammatory effect in mice treated with and without antibiotics. Orally administered baicalin showed the anti-inflammatory effect in mice than intraperitoneally treated one, apart from intraperitoneally administered its metabolites, baicalein and oroxylin A, which potently inhibited LPS-induced inflammation. Of these metabolites, oroxylin A showed more potent anti-inflammatory effect. However, treatment with the mixture of cefadroxil, oxytetracycline and erythromycin (COE) significantly attenuated the anti-inflammatory effect of orally administered baicalin in mice. Treatment with COE also reduced intestinal bacterial fecal ${\beta}$-glucuronidase activity. The metabolic activity of human stools is significantly different between individuals, but neither between ages nor between male and female. Baicalin was metabolized to baicalein and oroxylin A, with metabolic activities of $1.427{\pm}0.818$ and $1.025{\pm}0.603$ pmol/min/mg wet weight, respectively. Baicalin and its metabolites also inhibited the expression of pro-inflammatory cytokines, TNF-${\alpha}$ and IL-$1{\beta}$, and the activation of NF-${\kappa}B$B in LPS-stimulated peritoneal macrophages. Of them, oroxylin A showed the most potent inhibition. Based on these findings, baicalin may be metabolized to baicalein and oroxylin A by intestinal microflora, which enhance its anti-inflammatory effect by inhibiting NF-${\kappa}B$ activation.

• Biomolecules & Therapeutics
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• v.16 no.4
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• pp.394-402
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• 2008

Atopic dermatitis (AD) is an inflammatory skin disease commonly characterized by infiltration of inflammatory cells into skin lesions. Keratinocytes produce many chemokines that are involved in the pathogenesis of skin disorders. In particular, macrophage-derived chemokine (MDC/CCL22) and thymus and activationregulated chemokine (TARC/CCL17) are Th2-type cytokines. Serum MDC and TARC levels are increased in AD patients. In this study, we investigated the anti-inflammatory effect and mechanism of action of the active fraction from Prunus yedoensis bark. We evaluated their inhibitory effects on the AD-like inflammatory markers (MDC and TARC) and JAK-STAT pathway (STAT1) in HaCaT keratinocytes. The EtOAc fraction of the crude extract (80% EtOH) and the E5 sub-fraction potently inhibited the induction of MDC and TARC mRNA and protein at 50 ${\mu}g$/mL in HaCaT cells. In addition, the E5 sub-fraction inhibited the phosphorylation of STAT1 protein associated with IFN-$\gamma$ signaling transduction in a dose-dependent manner. Thus, P. yedoensis may have antiatopic activity by suppressing the inflammatory chemokines (MDC and TARC).

• Parasites, Hosts and Diseases
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• v.56 no.3
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• pp.237-245
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• 2018

Toxoplasma gondii can infect all the vertebrates including human, and leads to serious toxoplasmosis and considerable veterinary problems. T. gondii heat shock protein 60 (HSP60) is associated with the activation of antigen presenting cells by inducing initial immune responses and releasing inflammatory cytokines. It might be a potential DNA vaccine candidate for this parasite. A pVAX-HSP60 DNA vaccine was constructed and immune responses was evaluated in Kunming mice in this study. Our data indicated that the innate and adaptive immune responses was elicited by successive immunizations with pVAX-HSP60 DNA, showing apparent increases of CD3e+CD4+ and CD3e+CD8a+ T cells in spleen tissues of the HSP60 DNA-immunized mice ($24.70{\pm}1.23%$ and $10.90{\pm}0.89%$, P<0.05) and higher levels of specific antibodies in sera. Furthermore, the survival period of the immunized mice ($10.53{\pm}4.78day$) were significantly prolonged during the acute T. gondii infection. Decrease of brain cysts was significant in the experimental group during the chronic infection (P<0.01). Taken together, TgHSP60 DNA can be as a vaccine candidate to prevent the acute and chronic T. gondii infections.

• Reproductive and Developmental Biology
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• v.30 no.1
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• pp.27-34
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• 2006

This study was conducted to compare the reproduction ability of the wild type boar and recombinant human erythropoietin (hEPO) transgenic boar semen. Ejaculated boar semen was analyzed by flow cytometry, Elisa and IVF methods. In experiment 1, flow cytometric analysis showed that the live sperm ratio of transgenic boar sperm significantly lower (P<0.05) than that of wild type boar after incubation at 20, 22, 24 and 26 hr. In experiment 2, the presence and levels of various cytokines (IL-6, IL-10 and $TNF-{\alpha}$) to related animal reproduction in the seminal and blood plasma were examined using specific enzyme immunoassay. There was no significant difference between both groups. In experiment 3, the fertilizing capacity and developmental ability of both boar sperm were compared. The transgenic boar sperm had a significantly low capacity of penetration, sperm-zona binding, embryo development, and blastocyst formation compared to wild type sperm (P<0.05). These results suggest that transgenic boar sperm harboring hEPO gene has low sperm viability than wild type boar, and it is a reason to decrease of fertility and litter size.

• The Korean Journal of Food And Nutrition
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• v.27 no.3
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• pp.400-405
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• 2014

Recently, cases of Aloe vera induced-toxic hepatitis have been reported. However, the precise inflammatory effects of Aloe vera extract have not been clearly elucidated yet. In this study, the inflammatory effects and the mechanism of 70% ethanolic Aloe vera extract on liver were evaluated by in vitro assays using human hepatoma HepG2 cells. Cell viability was investigated using MTT assay at $0.001{\sim}100{\mu}g/mL$ of Aloe vera extract. To evaluate inflammatory effect of the Aloe vera extract, the secretion of pro-inflammatory cytokine Interleukin 8 (IL-8) and Macrophage colony-stimulating factor (M-CSF) were detected. Aloe vera extract did not induce cell death at concentrations of $0.001{\sim}100{\mu}g/mL$. However, Aloe vera extract significantly increased the IL-8 secretion by 15.7~25.8% and the M-CSF secretion by 36.6~61.5% at the same concentrations. These results indicate that Aloe vera extract shows an inflammation-related mild hepatotoxicity than a severe toxicity such as cell death and this hepatitis is mediated by the secretion of inflammatory cytokine IL-8 and M-CSF.