• The Korea Journal of Herbology
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• v.28 no.5
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• pp.61-68
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• 2013

Objectives : Hibisci Flos has long been used for inflammatory diseases in traditional Korean medicine. However, little scientific investigation has been carried out. The aim of the present study is to investigate the effect of Hibisci Flos water extract (HF) on inflammatory cytokines production in Raw 264.7 cells stimulated by lipopolysaccaride (LPS). Method : HF was prepared by extracting with boiling water for 2 hours. We observed the cell viability of mouse macrophage Raw 264.7, the production of nitric oxide (NO) and the inflammatory cytokines such as interleukin (IL)-4, IL-5, IL-10, IL-15, tumor necrosis factor-${\alpha}$ (TNF-${\alpha}$), interferon-gamma (IFN-${\gamma}$), vascular endothelial growth factor (VEGF), granulocyte macrophage-colony stimulating factor (GM-CSF), and macrophage colony-stimulating factor (M-CSF) in Raw 264.7 cells stimulated by LPS. Result : The MTT assay was carried out to check the cellular toxicity of HF. No significant toxicity was observed in the experiment. HF significantly inhibited the increase of NO in the macrophages induced by LPS after 24 hour treatment. HF significantly inhibited the production of IL-4, IL-5, IL-10, IL-15, TNF-${\alpha}$, IFN-${\gamma}$, VEGF, GM-CSF and M-CSF in the Raw 264.7 cells induced by LPS in the concentration of $25{\mu}g/mL$ or higher. Conclusion : These results suggest that HF might have regulatory effects on LPS-induced inflammatory cytokine production, which might explain its beneficial effect in the treatment of inflammatory disease.

• Journal of Veterinary Clinics
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• v.39 no.2
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• pp.51-58
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• 2022

Quercetin, a flavonoid found in fruits and vegetables, exhibits a strong anti-inflammatory activity. The objective of this study was to examine the effect of quercetin on chemotactic activity of peripheral blood polymorphonuclear cells (PMNs) to culture supernatant from peripheral blood mononuclear cells (PBMCs) stimulated with lipopolysaccharide (LPS). In addition, we determined whether this effect is related to interleukin (IL)-8 and changes in cytoskeleton. The chemotactic activity of PMNs was evaluated by a modified Boyden chamber assay. Total cellular filamentous (F)-actin levels were measured by method of fluorescence microscopy. The levels of IL-8 mRNA and protein were measured by real time polymerase reaction method and enzyme-linked immunosorbent assay, respectively. Quercetin (0-50 µM) itself has no chemoattractant effect for PMNs. The culture supernatant from PBMCs (2 × 10⁶ cells/mL) treated with LPS (1 ㎍/mL) showed remarkable increase in chemotaxis of PMNs. However, this effect was reduced dose-dependently by treatment with quercetin. In addition, PBMCs treated with LPS revealed enhanced levels in IL-8 protein and mRNA. Co-treatment of LPS with quercetin (50 µM) in PBMCs decreased IL-8 production and expression. Treatment of quercetin (0-50 µM) on PMNs to rpIL-8 (10 nM) decreased dose-dependently the chemotactic activity of PMNs. Treatment of quercetin on PMNs to IL-8 also reduced their total cellular F-actin level. These results suggested that quercetin attenuates chemotactic activity of PMNs, which is mediated by down-regulation of IL-8 production from LPS-stimulated PBMCs and inhibition of F-actin polymerization in PMNs.

• Journal of Embryo Transfer
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• v.31 no.4
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• pp.323-333
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• 2016

Pro-inflammatory cytokines, interleukin-$1{\beta}$(IL1B), IL6, and tumor necrosis factor-alpha (TNF), are known to play important roles in regulating the endometrial function in the uterus during the estrous cycle and pregnancy in several species. However, the expression and function of these cytokines and their receptors in the uterine endometrium during the estrous cycle have not been studied in pigs. Thus, this study determined the expression and regulation of IL1B, IL6, TNF and their respective receptors, IL1R1, IL1RAP, IL6R, GP130, TNFRSF1A, and TNFRSF1B during the estrous cycle in pigs. To analyze levels of each gene expression in the uterine endometrium we obtained from endometrial tissues on Days 0, 3, 6, 9, 12, 15, and 18 of the estrous cycle. Real-time RT-PCR analysis showed that levels of IL1B, IL1RAP, IL6R, GP130, TNF, TNFRSF1A, and TNFRSF1B mRNAs were highest on Day 15 or 18 of the estrous cycle, which corresponds to the proestrus period. Levels of IL1R1 were highest on Day 0, while levels of IL6 were biphasic with high levels on Day 6 and Day 15. The abundance of IL1B, IL6, IL6R, and TNF mRNAs was decreased by progesterone, while levels of GP130 were increased by progesterone in endometrial tissue explants. These results showed that expression of pro-inflammatory cytokines and their receptors changed stage-specifically during the estrous cycle and regulated by progesterone in the uterine endometrium in pigs, suggesting that these pro-inflammatory cytokines may be involved in the regulation endometrial function during the estrous cycle in pigs.

• Journal of Life Science
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• v.22 no.12
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• pp.1637-1643
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• 2012

This study investigated the effects of PG on IL-$1{\beta}$ expression and determined cellular factors involved in PG-mediated IL-$1{\beta}$ up-regulation in mononuclear cells in order to understand the molecular mechanisms underlying inflammatory responses associated with bacterial pathogen-associated molecular patterns in the diseased artery. Exposure of human monocytic leukemia THP-1 cells to PG resulted in enhanced secretion of IL-$1{\beta}$ and also profound induction of the IL-$1{\beta}$ gene transcript. These effects were abrogated by OxPAPC, an inhibitor of TLR-2/4. Pharmacological inhibitors such as U0126, SP6001250, Akti IV, rapamycin, and DPI also significantly attenuated PG-mediated IL-$1{\beta}$ up-regulation. However, polymyxin B did not influence the IL-$1{\beta}$ expression. This study indicates that PG contributes to vascular inflammation in atherosclerotic plaques by up-regulating expression of IL-$1{\beta}$ via TLR-2, Akt, mTOR, MAPKs, and ROS.

• Journal of Microbiology and Biotechnology
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• v.32 no.6
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• pp.792-799
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• 2022

As a vital problem in reproductive health, recurrent spontaneous abortion (RSA) affects about 1% of women. We performed this study with an aim to explore the molecular mechanism of interleukin-23 (IL-23) and find optimal or effective methods to improve RSA. First, ELISA was applied to evaluate the expressions of IL-23 and its receptor in HTR-8/SVneo cells after IL-23 treatment. CCK-8, TUNEL, wound healing and transwell assays were employed to assess the proliferation, apoptosis, migration and invasion of HTR-8/SVneo cells, respectively. Additionally, the expressions of apoptosis-, migration-, epithelial-mesenchymal transition- (EMT-) and p38 MAPK signaling pathway-related proteins were measured by western blotting. To further investigate the relationship between IL-23 and p38 MAPK signaling pathway, HTR-8/SVneo cells were treated for 1 h with p38 MAPK inhibitor SB239063, followed by a series of cellular experiments on proliferation, apoptosis, migration and invasion, as aforementioned. The results showed that IL-23 and its receptors were greatly elevated in IL-23-treated HTR-8/SVneo cells. Additionally, IL-23 demonstrated suppressive effects on the proliferation, apoptosis, migration, invasion and EMT of IL-23-treated HTR-8/SVneo cells. More importantly, the molecular mechanism of IL-23 was revealed in this study; that is to say, IL-23 inhibited the proliferation, apoptosis, migration, invasion and EMT of IL-23-treated HTR-8/SVneo cells via activating p38 MAPK signaling pathway. In conclusion, IL-23 inhibits trophoblast proliferation, migration, and EMT via activating p38 MAPK signaling pathway, suggesting that IL-23 might be a novel target for the improvement of RSA.

• Journal of Oral Medicine and Pain
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• v.41 no.3
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• pp.126-132
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• 2016

Purpose: The aims of this study were to analyze the association between inflammatory cytokine and obstructive sleep apnea (OSA), and to evaluate treatment outcome and changes of plasma inflammatory cytokine levels after oral appliance therapy. Methods: Twenty-seven subjects who visited Department of Oral Medicine in Seoul National University Dental Hospital were performed nocturnal polysomnography and analyzed plasma C-reactive protein (CRP), interleukin (IL)-$1{\beta}$, IL-6, IL-10, and tumor necrosis factor (TNF)-${\alpha}$ levels. Each subject was evaluated with Pittsburgh Sleep Quality Index (PSQI) and Epworth Sleepiness Scale (ESS). The subjects were classified into 12 OSA patients (apnea-hypopnea index [AHI] >5) and 15 control (AHI ${\leq}5$) groups. The OSA group was treated with mandibular advancement device (MAD) for 3 months and re-evaluated nocturnal polysomnography and plasma inflammatory cytokine levels. Results: Plasma TNF-${\alpha}$, IL-10, and IL-6 levels were significantly higher in OSA patients compared to controls. Total AHI showed significant positive correlations with plasma IL-6 and TNF-${\alpha}$ levels. Percentage time of $SpO_2$ <90 and lowest $SpO_2$ were significantly correlated with plasma TNF-${\alpha}$ level. ESS showed significant positive correlation with plasma IL-10 level. Total AHI, percentage time of $SpO_2$ <90, lowest $SpO_2$, and mean $SpO_2$ were significantly improved after the MAD therapy. Plasma TNF-${\alpha}$ level was significantly decreased after MAD therapy. Conclusions: We suggest that MAD therapy is an effective treatment modality for patients with OSA and can decrease plasma cytokine level.

• Journal of Periodontal and Implant Science
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• v.37 no.3
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• pp.563-573
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• 2007

Genetic polymorphisms associated with aggressive periodontitis have previously been reported. Interleukin-10 is an immunoregulatory cytokine that plays a role in the pathogenesis of periodontitis. Individual capacity for IL-10 production appears to be under genetic influence, The aim of present investigation was to explore possible genetic association of IL-10 gene promoter polymorphisms with generalized aggressive periodontitis. The study population consisted of 37 generalized aggressive periodontitis patients from the Department of Periodontology, Chonnam National University Hospital and 27 control subjects, all the subjects were non-smokers, Genomic DNA was obtained from buccal swab. The IL-10promoter -597, -824, -1082 positions were genotyped by amplifying the polymorphic regions using polymerase chain reaction (PCR) , followed by restriction enzyme digestion and gel electrophoresis. IL-10-597 C (allele 1) to A (allele 2) and IL-10-824 C (allele 1) to T (allele 2) and IL-10-1082 G (allele 1) to A (allele 2) polymorphisms were examined. The results were as follows. 1. In patients, the distribution of genotypes C/C, C/A and NA at Il-10-597 was determined to be 13.5%, 37.8% and 48.7%, respectively and the distribution of genotypes at IL-10-824 was the same as that of IL-10-597. The distribution of genotypes G/G, G/A and NA at IL-10-1082 was found to be 2.7%, 16.2% and 81. 4%, respectively. No statistical difference in genotype distribution was found between the patient and control groups. 2. Allele 2 carriage rate at the three position of the IL-10 promoter region was higher in the control group than the patient group. 3. Allele 2 frequencies at IL-10-597 and -824 positions were higher in female group than male group and its difference was statistically significant(p<0.05). No significant difference in genotype distribution between the control and patient groups. Allele frequency between control and patient groups was not significantly different although allele 2 frequency at the three positions in the IL-10 promoter region appeared to be higher in control group. In conclusion, no clear association between IL-10 gene promoter polymorphisms and generalized aggressive periodontitis in Korean was observed.

• Food Engineering Progress
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• v.22 no.4
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• pp.337-343
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• 2018

Coffee is a commonly consumed beverage that contains anti-inflammatory compounds such as caffeine, chlorogenic acid, cafestol, trigonelline, and kahweol. Lactobacillus plantarum is a lactic acid bacterium most frequently used in the fermentation of food products of plant origin. L. plantarum is able to degrade some food phenolic compounds and provide high value-added compounds such as powerful antioxidants or food additives approved as flavouring agents. In this study, we investigated the anti-inflammatory effects of coffee extract fermented by L. plantarum on RAW264.7 macrophages. In lipopolysaccharide-stimulated RAW264.7 cells, these coffee extracts exhibited anti-inflammatory activities through the reduction of nitric oxide (NO) production and inducible NO synthase expression. Fermented coffee extracts significantly decreased the expression of inflammatory cytokines such as tumor necrosis factor ${\alpha}$, interleukin $1{\beta}$, interleukin 6, and interferon ${\gamma}$. Cyclooxygenase-2, which is one of the key biomarkers for inflammation, was significantly suppressed. These results might be helpful for understanding the anti-inflammatory mechanism of fermented coffee extract on immune cells and, moreover, suggest that fermented coffee extract may be a beneficial anti-inflammatory agent.

• IMMUNE NETWORK
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• v.3 no.2
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• pp.136-144
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• 2003

Oral administration of antigen has long been considered as a promising alternative for the treatment of chronic autoimmune diseases including rheumatoid arthritis (RA), and oral application of type II collagen (CII) has been proven to improve pathogenic symptoms in RA patients without problematic side effects. To further current understandings about the immune suppression mechanisms mediated by orally administered antigens, we examined the changes in IgG subtypes, T-cell proliferative response, and proportion of interleukin (IL)-10 producing Th subsets in a time course study of collagen induced arthritis (CIA) animal models. We found that joint inflammation in CIA mouse peaked at 5 weeks after first immunization with CII, which was significantly subdued in mice pre-treated by repeated oral administration of CII. Orally tolerized mice also showed increase in their serum level of IgG1, while the level of IgG2a was decreased. T-cell proliferation upon CII stimulation was also suppressed in lymph nodes of mice given oral administration of CII compared to non-tolerized controls. When cultured in vitro in the presence of CII, T-cells isolated from orally tolerized mice presented higher proportion of $CD4^+IL-10^+$ subsets compared to non-tolerized controls. Interestingly, such increase in IL-10 producing cells were obvious first in Peyer's patch, then by 5 weeks after immunization, in mesenteric lymph node and spleen instead. This result indicates that a particular subset of T-cells with immune suppressive functions might have migrated from the original contact site with CII to inflamed joints via peripheral blood after 5 weeks post immunization.

• The Korea Journal of Herbology
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• v.35 no.1
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• pp.35-44
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• 2020

Objectives : The objective of this study was to investigate the therapeutic effect of Corni Fructus 30% ethanol extract (CFE) on the monosodium iodoacetate (MIA)-induced osteoarthritis rats. Methods : The subjects were divided into 4 groups ; Normal group (N, n=10), MIA-induced osteoarthritis control group (Con, n=10), indomethacin 5 mg/kg treated group (INDO, n=10), CFE 200 mg/kg treated group (CFE, n=10). Blood and articulation tissues were collected after two weeks of drug administration. Oxidative stress was analyzed with reactive oxygen species (ROS), peroxynitrite (ONOO-). And the Nuclear factor erythroid-2 (Nrf2), heme oxygenase-1 (HO-1), superoxide dismutase (SOD), catalase, glutathione peroxidase-1/2 (GPx-1/2), Nuclear Factor Kappa B p65 (NF-κBp65), cyclooxygenase-2 (COX-2), inducible nitric oxide synthase (iNOS), tumor necrosis factor-alpha (TNFα), interleukin-6 (IL-6), Interleukin 1β (IL-1β), matrix metalloproteinase-1 (MMP-1), and tissue inhibitor of metalloproteinases-1 (TIMP-1) were investigated by western blot. Results : The administration of CFE showed a significant reduction of changes in relative hind paw weight distribution. Reactive oxygen species (ROS) and peroxy nitrite (ONOO-) levels of articulation tissues were significantly decreased in CFE compared to the control group. Western blot measurements of Nrf2, HO-1, SOD, catalase, GPx-1/2 showed that the CFE group was increased compared to the Con group. And western blot measurements of NF-κBp65, COX-2, iNOS, TNFα, IL-6, IL-1β showed that the CFE group was reduced compared to the Con group. Also CFE group decreased MMP-1 and increased TIMP-1. Conclusion : Based on the above results, it can be seen that osteoarthritis is improved when Corni Fructus 30% ethanol extract treated.