• Molecules and Cells
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• v.46 no.10
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• pp.627-636
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• 2023

Periodontal disease is a chronic inflammatory disease that leads to the gradual destruction of the supporting structures of the teeth including gums, periodontal ligaments, alveolar bone, and root cementum. Recently, interests in alleviating symptoms of periodontitis (PD) using natural compounds is increasing. Avenanthramide-C (Avn-C) is a polyphenol found only in oats. It is known to exhibit various biological properties. To date, the effect of Avn-C on PD pathogenesis has not been confirmed. Therefore, this study aimed to verify the protective effects of Avn-C on periodontal inflammation and subsequent alveolar bone erosion in vitro and in vivo. Upregulated expression of catabolic factors, such as matrix metalloproteinase 1 (MMP1), MMP3, interleukin (IL)-6, IL-8, and COX2 induced by lipopolysaccharide and proinflammatory cytokines, IL-1β, and tumor necrosis factor α (TNF-α), was dramatically decreased by Avn-C treatment in human gingival fibroblasts and periodontal ligament cells. Moreover, alveolar bone erosion in the ligature-induced PD mouse model was ameliorated by intra-gingival injection of Avn-C. Molecular mechanism studies revealed that the inhibitory effects of Avn-C on the upregulation of catabolic factors were mediated via ERK (extracellular signal-regulated kinase) and NF-κB pathway that was activated by IL-1β or p38 MAPK and JNK signaling that was activated by TNF-α, respectively. Based on this study, we recommend that Avn-C may be a new natural compound that can be applied to PD treatment.

• Journal of Ginseng Research
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• v.41 no.2
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• pp.134-143
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• 2017

Background: The prevalence of allergic inflammatory diseases such as atopic dermatitis (AD), asthma, and allergic rhinitis worldwide has increased and complete recovery is difficult. Korean Red Ginseng, which is the heat-processed root of Panax ginseng Meyer, is widely and frequently used as a traditional medicine in East Asia. In this study, we investigated whether Korean Red Ginseng water extract (RGE) regulates the expression of proinflammatory cytokines and chemokines via the mitogen-activated protein kinases (MAPKs)/nuclear factor kappa B ($NF-{\kappa}B$) pathway in allergic inflammation. Methods: Compound 48/80-induced anaphylactic shock and 1-fluoro-2,4-dinitrobenzene (DNFB)-induced AD-like skin lesion mice models were used to investigate the antiallergic effects of RGE. Human keratinocytes (HaCaT cells) and human mast cells (HMC-1) were also used to clarify the effects of RGE on the expression of proinflammatory cytokines and chemokines. Results: Anaphylactic shock and DNFB-induced AD-like skin lesions were attenuated by RGE administration through reduction of serum immunoglobulin E (IgE) and interleukin (IL)-6 levels in mouse models. RGE also reduced the production of proinflammatory cytokines including $IL-1{\beta}$, IL-6, and IL-8, and expression of chemokines such as IL-8, thymus and activation-regulated chemokine (TARC), and macrophage-derived chemokine (MDC) in HaCaT cells. Additionally, RGE decreased the release of tumor necrosis $factor-{\alpha}$ ($TNF-{\alpha}$), $IL-1{\beta}$, IL-6, and IL-8 as well as expressions of chemokines including macro-phage inflammatory protein $(MIP)-1{\alpha}$, $MIP-1{\beta}$, regulated on activation, normal T cell expressed and secreted (RANTES), monocyte chemoattractant protein (MCP)-1, and IL-8 in HMC-1 cells. Furthermore, our data demonstrated that these inhibitory effects occurred through blockage of the MAPK and $NF-{\kappa}B$ pathway. Conclusion: RGE may be a useful therapeutic agent for the treatment of allergic inflammatory diseases such as AD-like dermatitis.

• Journal of Life Science
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• v.19 no.3
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• pp.299-304
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• 2009

Interleukin 27 (IL-27) was discovered as a heterodimeric cytokine of the IL-12 family, and is composed of two subunits - Epstein-Barr virus induced gene 3 (EBI3) and p28. It acts as a versatile cytokine in the early regulation of Th1 initiation and in the negative regulation of the Th2 factor GATA binding protein 3 (GATA-3). This cytokine is mediated by the IL-27 receptor (WSX-1), which is highly expressed on $CD4^+$ T lymphocytes and NK cells. We previously identified four polymorphisms in the human IL-27p28 gene and suggested that the polymorphism of IL-27p28 is associated with susceptibility to asthma. To determine whether these IL-27p28 SNPs are associated with susceptibility to allergic rhinitis, the genotype and allele frequencies of IL-27p28 SNPs were analyzed between allergic rhinitis patients and healthy controls. Although the genotype and allele frequencies of IL-27p28 SNPs in allergic rhinitis patients were not significantly different from those of the control group, there was a suggestive difference (P=0.037) between these groups in total serum IgE levels in the g.2905T>G SNP of the IL-27p28 gene. Our result implies that the g.2905T>G SNP of the IL-27p28 gene might have an affect on IgE production in allergic rhinitis patients.

• Clinical and Experimental Reproductive Medicine
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• v.37 no.2
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• pp.125-134
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• 2010

Objective: The aim of this study was to measure the concentrations of cytokines contained in the hydrosalpingeal fluid and to evaluate the effect on the mouse embryo development with the different cytokine concentration. Methods: The hydrosalpingeal fluids (HSF) were collected during the surgery for hydrosalpinx which was confirmed by hysterosalphingogram. The cytokines in HSF including interleukin (IL)-$1{\alpha}$, IL-$1{\beta}$, IL-2, IL-4, IL-6, IL-8, IL-10, TNF-$\alpha$, Interferon-$\gamma$ (IFN-$\gamma$), vascular endothelial growth factor (VEGF), epidermal growth factor (EGF), monocyte chemotactic protein-1 (MCP-1) were measured by ELISA method. HSF were added up to culture media with 5%, 10%, and 30% concentrations. The blastulation rates were compared. Results: IL-$\alpha$, IL-$1{\beta}$, IL-2, IL-4, IL-6, IL-8, IL-10, TNF-$\alpha$, IFN-$\bamma$, VEGF, EGF, and MCP-1 were detected, but the concentrations were different from each sample. IL-6 and IL-10 were increased in HSF-1 group, and IFN-$\gamma$, MCP-1, VEGF were increased in HSF-2 compared with normal serum range. The Th1/Th2 ratio of HSF-2 (IFN-$\gamma$:IL10) was highly elevated to 61.64, compared with that of HSF-1 (3.69). The blastulation rate was significantly decreased in HSF-2 group (27.7%) compared those of the HSF-1 group (74%) and control group (76.7%). It showed the trend that the blastulation rate was decreased depending on the concentration HSF of culture media in HSF-2 group, but it was not statistically significant. Conclusion: The composition and concentration of cytokines in each HSF were different, and increased proinflammatory cytokines in HSF might be associated with poor embryonic development. Further study will be needed about the effect of each cytokines in HSF.

• Korean Journal of Medicinal Crop Science
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• v.11 no.1
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• pp.5-12
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• 2003

The biological activities of extracts from Rubus coreanus Miq. were compared. About 70% of the growth of human hepatocarcinoma and 79% of human gastric cancer cell was inhibited in adding 1.0 mg/ml of the extracts of Rubus coreanus Miq. respectively. The growth of human breast cancer cells was also inhibited in adding 1.0 mg/ml of the extracts as well as 78% of the human cancer cells. It was proved that the growth of human normal lung cell, scored as 15% for the extracts. Overall selectivity of the extracts on several human cancer cell line was over 5, which is higher than those from the Rubus coreanus Miq. The growth of both human immune B and T cells was enhanced up to 1.4 to 1.8 times by adding the extracts, compared to the controls. The secretion of tumor necrosis $factor-alpha(TNF-{\alpha})$ from T cell was also increased up to 78.8 pg/ml in adding the ethanol extract (0.5 mg/ml). Ethanol extract also increased up to about 70 pg/ml of interleukin-6(IL-6) from B cell. For screening regulate function of blood pressure, angiotensin converting enzyme(ACE) activity was inhibited up to 25% by adding the ethanol extract (1.0 mg/ml). In testing the hypoglycemic activity, 20% of ${\alpha}-glucosidase$ activity was inhibited for the extracts (0.5 mg/ml). GST activity was increased in the range of 1.2 to 1.6 times by adding extracts.

• Tuberculosis and Respiratory Diseases
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• v.41 no.5
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• pp.452-461
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• 1994

Background: Tumor necrosis factor(TNF)-$\alpha$ and Interleukin(lL)-$1{\beta}$ are thought to play a major role in the pathogenesis of the septic syndrome, which is frequently associated with adult respiratory distress syndrome(ARDS). In spite of many reports for the role of TNF-$\alpha$ in the pathogenesis of ARDS, including human studies, it has been reported that TNF-$\alpha$ is not sensitive and specific marker for impending ARDS. But there is a possibility that the results were affected by the diversity of pathogenetic mechanisms leading to the ARDS because of various underlying disorders of the study group in the previous reports. The purpose of the present study was to evaluate the roles of TNF-$\alpha$ and IL-$1{\beta}$ as a predictable marker for development of ARDS in the patients with septic syndrome, in which the pathogenesis is believed to be mainly cytokine-mediated. Methods: Thirty-six patients of the septic syndrome hospitalized in the intensive care units of the Asan Medical Center were studied. Sixteens suffered from ARDS, whereas the remaining 20 were at the risk of developing ARDS(acute hypoxemic respiratory failure, AHRF). In all patients venous blood samples were collected in heparin-coated tubes at the time of enrollment, at 24 and 72 h thereafter. TNF-$\alpha$ and IL-$1{\beta}$ was measured by an enzyme-linked immunosorbent assay (ELISA). All data are expressed as median with interquartile range. Results: 1) Plama TNF-$\alpha$ levels: Plasma TNF-$\beta$ levels were less than 10pg/mL, which is lowest detection value of the kit used in this study within the range of the $mean{\pm}2SD$, in all of the normal controls, 8 of 16 subjects of ARDS and in 8 in 20 subjects of AHRF. Plasma TNF-$\alpha$ levels from patients with ARDS were 10.26pg/mL(median; <10-16.99pg/mL, interquartile range) and not different from those of patients at AHRF(10.82, <10-20.38pg/mL). There was also no significant difference between pre-ARDS(<10, <10-15.32pg/mL) and ARDS(<10, <10-10.22pg/mL). TNF-$\alpha$ levels were significantly greater in the patients with shock than the patients without shock(12.53pg/mL vs. <10pg/mL) (p<0.01). There was no statistical significance between survivors(<10, <10-12.92pg/mL) and nonsurvivors(11.80, <10-20.8pg/mL) (P=0.28) in the plasma TNF-$\alpha$ levels. 2) Plasma IL-$1{\beta}$ levels: Plasma IL-$1{\beta}$ levels were less than 0.3ng/mL, which is the lowest detection value of the kit used in this study, in one of each patients group. There was no significant difference in IL-$1{\beta}$ levels of the ARDS(2.22, 1.37-8.01ng/mL) and of the AHRF(2.13, 0.83-5.29ng/mL). There was also no significant difference between pre-ARDS(2.53, <0.3-8.34ngfmL) and ARDS(5.35, 0.66-11.51ng/mL), and between patients with septic shock and patients without shock (2.51, 1.28-8.34 vs 1.46, 0.15-2.13ng/mL). Plasma IL-$1{\beta}$ levels were significantly different between survivors(1.37, 0.4-2.36ng/mL) and nonsurvivors(2.84, 1.46-8.34ng/mL). Conclusion: Plasma TNF-$\alpha$ and IL-$1{\beta}$ level are not a predictable marker for development of ARDS. But TNF-$\alpha$ is a marker for shock in septic syndrome. These result could not exclude a possibility of pathophysiologic roles of TNF-$\alpha$ and IL-$1{\beta}$ in acute lung injury because these cytokine could be locally produced and exert its effects within the lungs.

• The Journal of Korean Obstetrics and Gynecology
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• v.15 no.4
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• pp.61-75
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• 2002

Recombinant human $interleukin-1{\beta}$ $(rhIL-1{\beta})$ regulates several activities of the osteoblast cells derived from mouse calvarial bone explants in vitro. $rhIL-1{\beta}$ stimulated cellular proliferation and the synthesis of prostaglandin $E_2(PGE_2)$ and plasminogen activator activity in the cultured cells in a dose-dependent manner. However, the induction of osteocalcin synthesis and alkaine phosphatase activity in response to vitamine D, two characteristics of the osteoblast phenotype, were antagonized by $rhIL-1{\beta}$ over a similar dose range. This study supports the role of $IL-1{\beta}$ in the pathological modulation of bone cell metabolism, with regard to implication in the pathogenesis of osteoporosis by $IL-1{\beta}$. When the mouse calvarial bone cells were used, the bone resorption induced by $IL-1{\beta}$ was strongly inhibited by calcitonin treatment, indicating osteoclast-mediated bone resorption. On the other hand, the medicinal extracts of Taeyoungjon-Jahage (T.Y.J-J.H.G extracts) was tested for whether they could inhibit $IL-1{\beta}-induced$ $PGE_2$ production. Cell viability was not significantly affected by treatment with the indicated concentration of the extracts. The T.Y.J.-J.H.G. extracts were shown to have the inhibitory effects against the synthesis of $PGE_2$. We also examined the effect of the pretreatment with a various concentrations of the T.Y.J.-J.H.G. extracts then treated the $PGE_2-induction$ agents. Pretreatment of the T.Y.J.-J.H.G. extracts for 1 h, which by itself had little effect on cell survival, did not enhance the synthesis of $PGE_2$. Furthermore, the T.Y.J-J.H.G. extracts were shown to have the protective effects against plasminogen dependent fibrinolysis induced by the bone resorption agents of $IL-1{\beta}$. Pretreatment of the T.Y.J.-J.H.G. extracts for 1 h did not enhance the plasminogen dependent fibrinolysis. Finally, calcitonin showed the inhibitory activity the $IL-1{\beta}-stimulated$ bone resorption in the mouse calvarial bone cells having both of the osteoblast and osteoclast cells. Seemingly, pretreatment of the T.Y.J.-J.H.G. extracts for 1 h reduced the bone resorption. These results clearly indicated that calcitonin and T.Y.J.-J.H.G. extracts play key roles in inhibition of the osteoclast-mediated bone resorption.

• Toxicological Research
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• v.34 no.2
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• pp.103-110
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• 2018

Environmental stimuli can lead to the excessive accumulation of reactive oxygen species (ROS), which is one of the risk factors for premature skin aging. Here, we investigated the protective effects of $7-MEGA^{TM}$ 500 (50% palmitoleic acid, 7-MEGA) against oxidative stress-induced cellular damage and its underlying therapeutic mechanisms in the HaCaT human skin keratinocyte cell line (HaCaT cells). Our results showed that treatment with 7-MEGA prior to hydrogen peroxide ($H_2O_2$)-induced damage significantly increased the viability of HaCaT cells. 7-MEGA effectively attenuated generation of $H_2O_2$-induced reactive oxygen species (ROS), and inhibited $H_2O_2$-induced inflammatory factors, such as prostaglandin $E_2$ ($PGE_2$), tumor necrosis $factor-{\alpha}$ ($TNF-{\alpha}$), and $interleukin-1{\beta}$ ($IL-1{\beta}$). In addition, cells treated with 7-MEGA exhibited significantly decreased expression of matrix metalloproteinase-1 (MMP-1) and increased expression of procollagen type 1 (PCOL1) and Elastin against oxidative stress by $H_2O_2$. Interestingly, these protective activities of 7-MEGA were similar in scope and of a higher magnitude than those seen with 98.5% palmitoleic acid (PA) obtained from Sigma when given at the same concentration (100 nL/mL). According to our data, 7-MEGA is able to protect HaCaT cells from $H_2O_2$-induced damage through inhibiting cellular oxidative stress and inflammation. Moreover, 7-MEGA may affect skin elasticity maintenance and improve skin wrinkles. These findings indicate that 7-MEGA may be useful as a food supplement for skin health.

• Biomolecules & Therapeutics
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• v.24 no.5
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• pp.529-535
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• 2016

Atopic dermatitis (AD) results from gene and environment interactions that lead to a range of immunological abnormalities and breakdown of the skin barrier. Protease-activated receptor 2 (PAR2) belongs to a family of G-protein coupled receptors and is expressed in suprabasal layers of the epidermis. PAR2 is activated by both trypsin and a specific agonist peptide, SLIGKV-$NH_2$ and is involved in both epidermal permeability barrier homeostasis and epithelial inflammation. In this study, we investigated the effect of lobaric acid on inflammation, keratinocyte differentiation, and recovery of the skin barrier in hairless mice. Lobaric acid blocked trypsin-induced and SLIGKV-$NH_2$-induced PAR2 activation resulting in decreased mobilization of intracellular $Ca^{2+}$ in HaCaT keratinocytes. Lobaric acid reduced expression of interleukin-8 induced by SLIGKV-$NH_2$ and thymus and activation regulated chemokine (TARC) induced by tumor necrosis factor-a (TNF-${\alpha}$) and IFN-${\gamma}$ in HaCaT keratinocytes. Lobaric acid also blocked SLIGKV-$NH_2$-induced activation of ERK, which is a downstream signal of PAR2 in normal human keratinocytes (NHEKs). Treatment with SLIGKV-$NH_2$ downregulated expression of involucrin, a differentiation marker protein in HaCaT keratinocytes, and upregulated expression of involucrin, transglutamase1 and filaggrin in NHEKs. However, lobaric acid antagonized the effect of SLIGKV-$NH_2$ in HaCaT keratinocytes and NHEKs. Topical application of lobaric acid accelerated barrier recovery kinetics in a SKH-1 hairless mouse model. These results suggested that lobaric acid is a PAR2 antagonist and could be a possible therapeutic agent for atopic dermatitis.

• Journal of Ginseng Research
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• v.36 no.2
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• pp.135-145
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• 2012

Previously, we reported that Helicobacter pylori-associated gastritis and gastric cancer are closely associated with increased levels of hydrogen sulfide ($H_2S$) and that Korean red ginseng significantly reduced the severity of H. pylori-associated gastric diseases by attenuating $H_2S$ generation. Because the incubation of endothelial cells with $H_2S$ has been known to enhance their angiogenic activities, we hypothesized that the amelioration of $H_2S$-induced gastric inflammation or angiogenesis in human umbilical vascular endothelial cells (HUVECs) might explain the preventive effect of Korean red ginseng on H. pylori-associated carcinogenesis. The expression of inflammatory mediators, angiogenic growth factors, and angiogenic activities in the absence or presence of Korean red ginseng extracts (KRGE) were evaluated in HUVECs stimulated with the $H_2S$ generator sodium hydrogen sulfide (NaHS). KRGE efficiently decreased the expression of cystathionine ${\beta}$-synthase and cystathionine ${\gamma}$-lyase, enzymes that are essential for $H_2S$ synthesis. Concomitantly, a significant decrease in the expression of inflammatory mediators, including cyclooxygenase-2 and inducible nitric oxide synthase, and several angiogenic factors, including interleukin (IL)-8, hypoxia inducible factor-1a, vascular endothelial growth factor, IL-6, and matrix metalloproteinases, was observed; all of these factors are normally induced after NaHS. An in vitro angiogenesis assay demonstrated that NaHS significantly increased tube formation in endothelial cells, whereas KRGE pretreatment significantly attenuated tube formation. NaHS activated p38 and Akt, increasing the expression of angiogenic factors and the proliferation of HUVECs, whereas KRGE effectively abrogated this $H_2S$-activated angiogenesis and the increase in inflammatory mediators in vascular endothelial cells. In conclusion, KRGE was able to mitigate $H_2S$-induced angiogenesis, implying that antagonistic action against $H_2S$-induced angiogenesis may be the mechanism underlying the gastric cancer preventive effects of KRGE in H. pylori infection.