• BMB Reports
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• v.56 no.6
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• pp.359-364
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• 2023

KAI1/CD82, a membrane tetraspanin protein, can prevent various cancers and retinal disorders through its anti-angiogenic and anti-metastatic capacity. However, little is known about its anti-inflammatory effect and molecular mechanism. Therefore, the present study aimed to inLPSvestigate effect of a recombinant protein of the large extracellular domain of human KAI1 (Gly 111-Leu 228, rhKAI1) on lipopolysaccharides (LPS)-stimulated RAW264.7 macrophage-like cells and mouse bone marrow-derived macrophages (BMDM) and to identify its underlying mechanism. Our data showed that rhKAI1 suppressed expression levels of classically macrophages (M1) phenotype-related surface markers F4/80+CD86+ in LPS-stimulated BMDM and RAW264.7 cells. In addition, LPS markedly increased mRNA expression and release levels of pro-inflammatory cytokines and mediators such as interleukin (IL)-1β, IL-6, tumor necrosis factor-α, cyclooxygenase-2, nitric oxide and prostaglandin E2, whereas these increases were substantially down-regulated by rhKAI1. Furthermore, LPS strongly increased expression of NF-κB p65 in the nuclei and phosphorylation of ERK, JNK, and p38 MAPK. However, nuclear translocation of NF-κB p65 and phosphorylation of JNK were greatly reversed in the presence of rhKAI1. Especially, rhKAI1 markedly suppressed expression of toll-like receptor (TLR4) and prevented binding of LPS with TLR4 through molecular docking predict analysis. Importantly, Glu 214 of rhKAI1 residue strongly interacted with Lys 360 of TLR4 residue, with a binding distance of 2.9 Å. Taken together, these findings suggest that rhKAI1 has an anti-inflammatory effect on LPS-polarized macrophages by interacting with TLR4 and down-regulating the JNK/NF-κB signaling pathway.

• Asian-Australasian Journal of Animal Sciences
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• v.33 no.7
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• pp.1156-1166
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• 2020

Objective: The aim of this study was to evaluate the effects of compound organic acid calcium (COAC) on growth performance, hepatic antioxidant status and intestinal barrier of male broilers under high ambient temperature (32.7℃). Methods: Nine hundred healthy one-d-old Cobb-500 male broiler chicks were randomly assigned into three groups with six replicates of 50 birds each. A basal diet supplemented with 0% (control), 0.4% and 0.8% COAC, respectively were fed to birds for 6 weeks. All treatments were under high ambient indoor temperature of 32.7℃, and had a constant calcium and available phosphorus ratio. Results: The results showed that, compared with control, the average daily gain of broilers in 0.4% and 0.8% was significantly increased and the ratio of feed to gain in in 0.4% and 0.8% was significantly decreased at 1 to 21, 22 to 42 and 1 to 42 days of age (p<0.05). Compared with control, 0.8% COAC slightly decreased (p = 0.093) the content of malondialdehyde in liver at 42 days of age while 0.4% COAC significantly decreased (p<0.05) the activity of alkaline phosphatase. Furthermore, 0.4% COAC significantly enhanced the intestinal barrier function via increasing jejunal and ileal ocln transcription, promoting jejunal mucin 2 transcription at 42 days of age (p<0.05), and decreasing jejunal toll-like receptor 2 (TLR-2) and ileal TLR-15, inducible nitric oxide synthase compared with control group (p<0.05). Whereas, no significant differences on the transcription of interleukin-1β in jejunum and ileum were observed among three treatments (p>0.05). Overall, heat stress caused by high natural environment temperature may induce the damage to hepatic antioxidation and intestinal barrier. Conclusion: Dietary inclusion of COAC can improve the tolerance of broilers to thermal environment through the modification of antioxidative parameters in liver and the mRNA expression of genes in intestinal barrier, resulting in an optimal inclusion level of 0.4%.

• Journal of the Korean Society of Food Science and Nutrition
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• v.43 no.3
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• pp.349-354
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• 2014

Elevation of intracellular calcium ($Ca^{{+}{+}}$) triggers degranulation of mast cells by bypassing receptor activation. Flos Sophora japonica L. has been used as a natural dying source and has been reported to have biological activities such as anti-inflammatory and anti-allergic effects through $Fc{\varepsilon}RI$ and IgE crosslinking. In the present investigation, we report the regulatory effect of ethanolic extract of Flos Sophora japonica L. (S.F) on allergic mediators produced by $Ca^{{+}{+}}$ ionophore activation in mast cells. S.F significantly inhibited calcium ionophore (A23187)-induced interleukin (IL)-4 and tumor necrosis factor (TNF)-${\alpha}$ production as well as mast cell degranulation. Furthermore, administration of S.F suppressed allergic reactions in a 2,4-dinitrofluorobenzene (DNFB)-induced allergic dermatitis mouse model. Both oral administration and ear painting using 50 mg/kg of S.F significantly reduced levels of cytokines such as IL-4, TNF, and interferon-${\gamma}$ in ear tissues compared to the DNFB alone-treated group. Serum IgE level in the S.F-treated group also decreased compared to the DNFB alone-treated group. Weights of spleens and lymph nodes in the S.F-treated groups also decreased compared to the control group. Considering the data, we conclude that S.F mediates its anti-allergic effects not only through $Fc{\varepsilon}RI$ stimulation but also $Ca^{{+}{+}}$ influx in mast cells.

• Clinical and Experimental Pediatrics
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• v.52 no.4
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• pp.435-440
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• 2009

Purpose : The concentration of soluble transferrin receptor (sTfR) is estimated as an iron parameter to evaluate erythropoiesis and iron status. The aim of our study is to evaluate the correlation between sTfR concentration and inflammatory parameters and to distinguish iron deficiency anemia from anemia of inflammation. Methods : One hundred and forty-four infants younger than two years of age who visited Gyeongsang University Hospital for 7 years from 2000 to 2006 were enrolled. Patients who had hemoglobin (Hb) <11 g/dL and ferritin <12 mg/L were excluded. Routine hematologic lab, serum ferritin, sTfR, and inflammatory markers [C-reactive protein(CRP), interleukin-6(IL-6), and absolute neutrophil count (ANC)] were investigated. Results : In all patients, the sTfR concentration showed a correlation with Hb, ferritin, MCV, and ANC, but not with CRP and IL-6. In multiple regression models, positive correlations were found between sTfR concentration and IL-6 (r=0.078, P=0.043), and negative correlations were found between sTfR concentration and ANC (r=-0.117, P=0.033) and MCV (r=-0.027, P=0.009). Conclusion : sTfR concentration was influenced by inflammatory parameters. Therefore, sTfR does not appear to be a useful parameter for discriminating between iron deficiency anemia and anemia of inflammation in infants.

• Journal of Ginseng Research
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• v.38 no.3
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• pp.167-172
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• 2014

Background: Roles of immune reaction and toll-like receptor-4 (TLR-4) have widely been established in the pathogenesis of alcoholic liver disease (ALD). Methods: We evaluated the biologic efficacy of Korean Red Ginseng (KRG), urushiol, and probiotics (Lactobacillus rhamnosus R0011 and Lactobacillus acidophilus R0052) in mouse models of ALD. Sixty C57BL/6 mice were equally divided into six feeding groups for 10 weeks: normal diet, alcohol, control, alcohol + KRG, alcohol + urushiol, and alcohol + probiotics. Alcohol was administered via a LiebereDeCarli liquid diet containing 10% alcohol. TLR-4 expression, proinflammatory cytokines, and histology, as well as the results of liver function tests were evaluated and compared. Results: No between-group differences were observed with regard to liver function. TLR-4 levels were significantly lower in the KRG, urushiol, and probiotics groups than in the alcohol group ($0.37{\pm}0.06ng/mL$, $0.39{\pm}0.12ng/mL$, and $0.33{\pm}0.07ng/mL$, respectively, vs. $0.88{\pm}0.31ng/mL$; p < 0.05). Interleukin-$1{\beta}$ levels in liver tissues were decreased among the probiotics and KRG groups. The tumor necrosis factor-${\alpha}$ level of liver tissue was decreased in the KRG group. Conclusion: The pathological findings showed that alcohol-induced steatosis was significantly reduced by KRG and urushiol. As these agents improve immunologic capacity, they may be considered in potential anti-ALD treatments.

• Journal of Chitin and Chitosan
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• v.23 no.4
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• pp.277-284
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• 2018

In this study, we investigated the anti-allergic effect of the ethyl acetate fraction of Ecklonia cava (EC-EtoAc) on the immunoglobulin E (IgE)/bovine serum albumin (BSA)-mediated activation of bone marrow-derived cultured mast cells (BMCMCs). We revealed that the $62.5{\mu}g/ml$ of EC-fractions ($EC-CHCl_3$, EC-Hexane and EC-EtoAc) inhibited IgE/BSA-activated ${\beta}$-hexosaminidase release from BMCMCs without cytotoxicity. Especially, EC-EtoAc showed the higher ${\beta}$-hexosaminidase release than the others. Also, EC-EtoAc reduced the expression levels of cytokines such as interleukin (IL)-$1{\beta}$, IL-4, IL-5, IL-6, IL-10, IL-13, interferon (IFN)-${\gamma}$ and tumor necrosis factor (TNF)-${\alpha}$ and a chemokine, thymus- and activation-regulated chemokine (TARC), compared to the only IgE/BSA-treated BMCMCs. Furthermore, EC-EtoAc significantly prevented the binding of IgE to Fc epsilon receptor $(Fc{\varepsilon}R)I$ and reduced the $Fc{\varepsilon}RI$ expression on the sensitized BMCMCs. Taken together, these results suggest that E. cava may be the natural agent with beneficial potentials for the treatment of type I allergic diseases induced by mast cell activation.

• Journal of Life Science
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• v.26 no.4
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• pp.431-438
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• 2016

The tumour necrosis factor (TNF)-related apoptosis-inducing ligand (TRAIL) is considered a promising anticancer agent due to its unique ability to induce cancer cell death having only negligible effects on normal cells. However, many cancer cells tend to be resistant to TRAIL. In this study, we investigated the effects and molecular mechanisms of sodium butyrate (SB), a histone deacetylase inhibitor, in sensitizing TRAIL-induced apoptosis in 5637 human bladder cancer cells. Our results indicated that co-treatment with SB and TRAIL significantly increased the apoptosis induction, compared with treatment with either agent alone. Co-treatment with SB and TRAIL effectively increased the cell-surface expression of death receptor (DR) 5, but not DR4, which was associated with the inhibition of cellular Fas-associated death domain (FADD)-like interleukin-1β-converting enzyme (FLICE) inhibitory protein (c-FLIP). Furthermore, the activation of caspases (caspase-3, -8 and -9) and degradation of poly(ADP-ribose) were markedly increased in 5637 cells co-treated with SB and TRAIL; however, the synergistic effect was perfectly attenuated by caspase inhibitors. We also found that combined treatment with SB and TRAIL effectively induced the expression of pro-apoptotic Bax, cytosolic cytochrome c and cleave Bid to truncated Bid (tBid), along with down-regulation of anti-apoptotic Bcl-xL expression. These results collectively suggest that a combined regimen of SB plus TRAIL may offer an effective therapeutic strategy for safely and selectively treating TRAIL-resistant bladder cancer cells.

• Korean Journal of Fisheries and Aquatic Sciences
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• v.48 no.4
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• pp.439-446
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• 2015

Inflammation is a protective response to infection or injury. However, prolonged inflammation can contribute to the pathogenesis of many diseases, such as cancer, diabetes, arthritis, atherosclerosis, and Alzheimer's disease. Recent studies have shown that activated macrophages, inflammatory effector cells, can react to tissue insults in a polarized manner, in which their phenotypes are polarized into two major subtypes, categorized as M1 or M2. Classical M1 activation involves the production of pro-inflammatory cytokines, such as interleukin (IL)-6 and tumor necrosis factor (TNF)-${\alpha}$, and free radicals, while M2 or alternative activation is an anti-inflammatory phenotype involved in homeostatic processes, such as wound healing, debris scavenging, and the dampening of inflammation via the production of very low levels of pro-inflammatory cytokines and high levels of anti-inflammatory mediators, including IL-10. As part of our ongoing effort to isolate anti-inflammatory compounds from seaweeds, we investigated the effects of phlorotannins isolated from the brown alga Ecklonia stolonifera on macrophage polarization. Mouse peritoneal macrophages were treated with various concentrations of the extracts, and real-time RT-PCR analyses were performed to examine the expression of polarization markers: IL-$1{\beta}$, IL-6, and TNF-${\alpha}$ for M1 and arginase-1, peroxisome proliferator-activated receptor (PPAR)-${\gamma}$, found inflammatory zone-1 (Fizz-1), chitinase 3-like 3 (Ym1), and$Kr{\ddot{u}}ppel$-like factor 4 (Klf-4) for M2. The pretreatment of cells with eckol, dieckol, and phlorofucofuroeckol-A (PFF-A), isolated from the ethyl acetate fraction of E. stolonifera ethanolic extract, potentiated the anti-inflammatory M2 phenotype of the macrophages. These results indicate that phlorotannins derived from E. stolonifera can be used to enrich macrophages with markers of the M2 anti-inflammatory state.

• Nutrition Research and Practice
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• v.12 no.3
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• pp.191-198
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• 2018

BACKGROUD/OBJECTIVES: Neuroinflammation plays critical role in neurodegenerative disorders, such as Alzheimer's disease (AD). We investigated the effect of three licorice varieties, Glycyrhiza uralensis, G. glabra, and Shinwongam (SW) on a mouse model of inflammation-induced memory and cognitive deficit. MATERIALS/METHODS: C57BL/6 mice were injected with lipopolysaccharide (LPS; 2.5 mg/kg, intraperitoneally) and orally administrated G. uralensis, G. glabra, and SW extract (150 mg/kg/day). SW, a new species of licorice in Korea, was combined with G. uralensis and G. glabra. Behavioral tests, including the T-maze, novel object recognition and Morris water maze, were carried out to assess learning and memory. In addition, the expressions of inflammation-related proteins in brain tissue were measured by western blotting. RESULTS: There was a significant decrease in spatial and objective recognition memory in LPS-induced cognitive impairment group, as measured by the T-maze and novel object recognition test; however, the administration of licorice ameliorated these deficits. In addition, licorice-treated groups exhibited improved learning and memory ability in the Morris water maze. Furthermore, LPS-injected mice had up-regulated pro-inflammatory proteins, such as inducible nitric oxide synthase (iNOS), cyclooxygenase-2, interleukin-6, via activation of toll like receptor 4 (TLR4) and nuclear factor-kappa B ($NF{\kappa}B$) pathways in the brain. However, these were attenuated by following administration of the three licorice varieties. Interestingly, the SW-administered group showed greater inhibition of iNOS and TLR4 when compared with the other licorice varieties. Furthermore, there was a significant increase in the expression of brain-derived neurotrophic factor (BDNF) in the brain of LPS-induced cognitively impaired mice that were administered licorice, with the greatest effect following SW treatment. CONCLUSIONS: The three licorice varieties ameliorated the inflammation-induced cognitive dysfunction by down-regulating inflammatory proteins and up-regulating BDNF. These results suggest that licorice, in particular SW, could be potential therapeutic agents against cognitive impairment.

• Nutrition Research and Practice
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• v.15 no.6
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• pp.798-806
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• 2021

BACKGROUND/OBJECTIVES: Obesity is associated with chronic inflammation. The spleen is the largest organ of the lymphatic system and has an important role in immunity. Obesity-induced inflammatory responses are triggered by Toll-like receptor (TLR)-myeloid differentiation primary response 88 (MyD88) pathway signaling. Phenethyl isothiocyanate (PEITC) and 3,3'-diindolylmethane (DIM), major dietary glucosinolates present in cruciferous vegetables, have been reported to produce anti-inflammatory effects on various diseases. However, the effects of PEITC and DIM on the obesity-induced inflammatory response in the spleen are unclear. The purpose of this study was to examine the anti-inflammatory effects of PEITC and DIM on the spleen and their mechanism in high fat/cholesterol diet (HFCD)-fed C57BL/6 mice. MATERIALS/METHODS: We established an animal model of HFCD-induced obesity using C57BL/6 mice. The mice were divided into six groups: normal diet with AIN-93G diet (CON), high fat diet (60% calories from fat) with 1% cholesterol (HFCD), HFCD with PEITC 30 mg/kg/day or 75 mg/kg/day (HFCD+P30, HFCD+P75), and HFCD with DIM 1.5 mg/kg/day or 7.5 mg/kg/day (HFCD+D1.5, HFCD+D7.5). Enzyme-linked immunosorbent assay was used to evaluate pro-inflammatory cytokine secretion. Western blot and quantitative polymerase chain reaction were used to analyze protein and mRNA levels of nuclear factor kappa B (NF-κB) p65, interleukin 6 (IL-6), cyclooxygenase 2 (COX-2), TLR2, TLR4, and MyD88 in spleen tissue. RESULTS: Serum IL-6 levels were significantly higher in the HFCD group than in groups fed a HFCD with PEITC or DIM. Levels of NF-κB p65 protein and TLR2/4, MyD88, NF-κB p65, IL-6, and COX-2 mRNA were significantly higher in the HFCD group than in the CON group and were reduced by the PEITC and DIM supplements. CONCLUSIONS: PEITC- and DIM-supplemented diets improved splenic inflammation by modulating the TLR2/4-MyD88 pathway in HFCD-fed mice. We suggest that dietary glucosinolates may at least partially improve obesity-induced inflammation of the spleen.