• Journal of Periodontal and Implant Science
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• 제37권3호
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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.

• 한국식품영양과학회지
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• 제44권2호
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• pp.182-190
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• 2015

본 연구는 홍삼추출물(홍삼단)과 생약복합추출물(헤모힘)이 주요 기능성분은 다르지만 면역활성이라는 생리활성 측면에서 동일한 효과를 인정하고 있어서 이들의 병용 처리가 면역세포에 어떠한 영향을 미치는지에 대해 알아보기 위하여 수행되었다. 면역활성능에 관한 평가를 진행하기 위하여 마우스의 골수에서 분리한 미분화 골수세포를 선천면역에서 중요한 역할을 수행하는 대식세포 및 수지상세포로 분화시킨 후 홍삼추출물과 생약복합추출물을 병용 처리하였을 때 대식세포 및 수지상세포의 세포 증식능 및 사이토카인의 분비능이 증가되는 것으로 관찰되었다. 또한 활성화된 탐식(면역)세포의 세포 표면에서 발현되는 CD80과 CD86의 발현과 탐식(면역)세포의 항원제시에 밀접한 관련이 있는 주 조직적합성 복합체(MHC class II)의 발현이 홍삼추출물과 생약복합추출물의 병용 처리구에서 유의적으로 증가되는 것으로 관찰되었다. 또한 후천면역에서 중요한 역할을 수행하는 면역 T 세포가 다량으로 분포하는 비장 조직으로부터 비장세포를 분리하여 홍삼추출물과 생약복합추출물을 병용처리하였을 때 세포 증식능 및 면역활성을 유도하는 Th1 세포가 분비하는 사이토카인의 함량이 증가되는 것으로 나타났다. 이러한 결과로 미루어 볼 때 홍삼추출물과 생약복합 추출물의 병용 처리는 선천면역뿐만 아니라 후천면역에 관여하는 다양한 면역세포의 활성화에 직 간접적으로 다양한 상승작용을 미치는 것으로 사료된다.

• 생명과학회지
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• 제26권11호
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• pp.1282-1288
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• 2016

본 연구는 섬애약쑥의 생리활성 규명을 위한 연구의 일환으로 물 추출물의 항염증 활성 및 간 염증에 대한 보호효과를 세포수준에서 확인하였다. 세포독성이 없는 $100{\sim}400{\mu}g/ml$의 농도 범위에서 섬애약쑥 추출물은 HepG2 세포에서 nitric oxide (NO)와 reactive nitrogen species (ROS)생성을 농도의존적으로 저해하였으며, 간염질환과 밀접한 관계가 있는 cytokine인 M-CSF와 IL-8의 발현을 감소시켰다. 또한 직접적인 간 손상을 나타낼 수 있는 지표인 AST와 ALT의 발현을 유의성 있게 감소시키는 결과를 얻을 수 있었다. 본 실험을 통해서 섬애약쑥물 추출물은 세포독성이 없는 $200{\sim}400{\mu}g/ml$의 범위에서 농도의존적으로 간 염증의 개선 효과를 가질 것이라는 단서를 확인하였다.

• Molecules and Cells
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• 제41권4호
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• pp.282-289
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• 2018

Interleukin-17A (IL-17A) is a pro-inflammatory cytokine mainly derived from T helper 17 cells and is known to be involved in the pathogenesis of chronic obstructive pulmonary disease (COPD). Cigarette smoke (CS) has been considered as a primary risk factor of COPD. However, the interaction between CS and IL-17A and the underlying molecular mechanisms have not been clarified. In the current study, we investigated the effects of cigarette smoke extract (CSE) on IL-17A-induced IL-8 production in human bronchial epithelial cells, and sought to identify the underlying molecular mechanisms. IL-8 production was significantly enhanced following treatment with both IL-17A and CSE, while treatment with either IL-17A or CSE alone caused only a slight increase in IL-8 production. CSE increased the transcription of IL-17RA/RC and surface membrane expression of IL-17R, which was suppressed by an inhibitor of the phosphoinositide 3-kinase (PI3K)/Akt pathway (LY294002). CSE caused inactivation of glycogen synthase $kinase-3{\beta}$ ($GSK-3{\beta}$) via the PI3K/Akt pathway. Blockade of $GSK-3{\beta}$ inactivation by overexpression of constitutively active $GSK-3{\beta}$ (S9A) completely suppressed the CSE-induced up-regulation of IL-17R expression and the CSE-induced enhancement of IL-8 secretion. In conclusion, inactivation of $GSK-3{\beta}$ via the PI3K/Akt pathway mediates CSE-induced up-regulation of IL-17R, which contributes to the enhancement of IL-17A-induced IL-8 production.

• 대한약침학회지
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• 제20권2호
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• pp.127-131
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• 2017

Objectives: Polymorphonuclear neutrophils (PMNs) constitute the first line of defense against invading microbial pathogens. Early events in inflammation involve the recruitment of neutrophils to the site of injury or damage where changes in intracellular calcium can cause the activation of pro-inflammatory mediators from neutrophils including superoxide generation, degranulation and release of myeloperoxidase (MPO), productions of interleukin (IL)-8 and tumor necrosis factor ${\alpha}$ ($TNF-{\alpha}$), and adhesion to the vascular endothelium. To address the anti-inflammatory role of flavonoids, in the present study, we investigated the effects of the flavonoids quercetin and vitexin on the stimulus-induced nitric oxide (NO), $TNF-{\alpha}$, and MPO productions in human neutrophils. Methods: Human peripheral blood neutrophils were isolated, and their viabilities were determined by using the Trypan Blue exclusion test. The polymorphonuclear leukocyte (PMNL) preparations contained more than 98% neutrophils as determined by morphological examination with Giemsa staining. The viabilities of cultured neutrophils with various concentrations of quercetin and vitexin ($1-100{\mu}M$) were studied using 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide (MTT) assays. Neutrophils were cultured in complete Roswell Park Memorial Institute (RPMI) medium, pre-incubated with or without quercetin and vitexin ($25{\mu}M$) for 45 min, and stimulated with phorbol 12-myristate 13-acetate (PMA) ($10^{-7}M$). NO production was carried out through nitrite determination by using the Griess method. Also, the $TNF-{\alpha}$ and the MPO productions were measured using enzyme-linked immunosorbent assay (ELISA) kits and MPO assay kits. Results: Neutrophil viability was not affected up to a concentration of $100{\mu}M$ of quercetin or vitexin. Both quercetin and vitexin significantly inhibited $TNF-{\alpha}$, NO, and MPO productions in human neutrophils (P < 0.001). Conclusion:The present study showed that both quercetin and vitexin had significant anti-inflammatory effects. Thus, treatment with either quercetin or vitexin may be considered as a therapeutic strategy for treating patients with neutrophil-mediated inflammatory diseases.

• 생물정신의학
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• 제6권2호
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• pp.227-234
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• 1999

자살 시도군 231명, 환자 대조군 231명, 정상대조군 231명을 대상으로 혈청 콜레스테롤 농도를 측정하여 다음의 결과를 얻었다. 1) 자살 시도군이 환자대조군 혹은 정상대조군보다 혈청 콜레스테롤 농도의 유의한 저하를 보였다. 2) 진단별로는 우울증과 인격장애에서 자살 시도군이 환자대조군보다 콜레스테롤 농도의 유의한 저하를 보였으나, 정신분열병과 양극성 정동장애 조증형에선 차이가 없었다. 3) 자살 시도군의 남녀별로 비교시, 남자가 여자보다 콜레스테롤 농도의 유의한 저하를 보였으며, 진단별로는 우울증에서만 유의한 차이를 보였다. 4) 자살 시도군에서 낮은 콜레스테롤 농도는 심각한 자살 수행과 연관성이 있었다. 5) 자살 시도군에서 치료전에 비해 치료후 혈청 콜레스테롤 농도의 유의한 증가를 보였다. 본 연구의 결과는 자살 시도의 예측인자로서 혈청 콜레스테롤이 이용될 수 있음을 시사한다. 향후 콜레스테롤 농도에 미치는 변인들을 통제한 전향적 방법을 통해 원인적 측면에서 혈청 콜레스테롤 농도와 세로토닌, 인터루킨-2, 멜라토닌 간의 연관성에 관한 연구가 이루어져야 하겠다.

• 동의생리병리학회지
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• 제27권1호
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• pp.83-91
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• 2013

Pruritus is a unpleasant symptom in the skin that provokes the act of or desire to scratch. Mast cells are important effector cells in allergic reactions such as pruritus and inflammation. The purpose of this study was undertaken to investigate the synergic anti-pruritic and anti-inflammatory effects of Scutellariae Radix (SB) plus Flos Loncerae (FL) extracts in rat peritoneal mast cells (RPMCs), pruritogen-induced scratching mice and 2,4-dinitrofluorobenzene (DNFB)-induced allergic mice. We investigated the effect of SB, FL and SB plus FL extracts on the production of tumor necrosis factor (TNF)-${\alpha}$, interleukin (IL)-$1{\beta}$, and histamine in RPMCs, on the scratching behavior in ICR mice, and skin clinical serverity and inflammatory mediators in DNFB-induced allergic hairless mice. RPMCs stimulated with PMA plus A23187 or compound 48/80 significantly increased TNF-${\alpha}$, IL-$1{\beta}$ or histamine production compared with media control. However, TNF-${\alpha}$ IL-$1{\beta}$ or histamine levels increased by PMA plus A23187 or compound 48/80 treatment were significantly inhibited by SB, FL in a dose-dependent manner. Especially, SB plus FL pretreatment had a synergic inhibitory effects on stimulator-induced cytokines (TNF-${\alpha}$ and IL-$1{\beta}$) and histamine production. Moreover, SB plus FL administration had a synergic inhibitory effects on the scratching behavior induced by pruritogen (compound 48/80, histamine, serotonin, substance P) in ICR mice. Furthermore, SB plus FL administration had a synergic inhibitory effects on skin damage, inflammatory mediators, leukocyte and mast cell infiltration induced by DNFB in hairless mice. These results suggest that SB plus FL administration has a potential use as a medicinal plant for treatment against itching and inflammation-related skin disease.

• Journal of Microbiology and Biotechnology
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• 제18권9호
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• pp.1606-1612
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• 2008

Interleukin (IL)-32 is a recently identified proinflammatory cytokine that is one of the IL-18 inducible genes, and plays an important role in autoimmune and inflammatory diseases. We produced antibodies against IL-32 and studied the expression of IL-32 in human stomach cancer. We detected IL-32 secreted from K-562 cells which were stably transfected with IL-32 and in the sera of stomach cancer patients by a sandwich ELISA using a monoclonal antibody KU32-52 and a polyclonal antibody. In order to optimize a sandwich immunoassay, recombinant IL-32a was added, followed by the addition of a biotinylated KU32-52 into microtiter plate wells precoated with a goat anti-IL-32 antibody. The bound biotinylated KU32-52 was probed with a streptavidin conjugated to HRP. This sandwich ELISA was highly specific and had a minimal detection limit of 80 pg/ml (mean${\pm}$SD of zero calibrator) and measuring up to 3,000 pg/ml. This ELISA showed no cross-reaction with other cytokines such as hIL-1$\alpha$, hIL-1$\beta$, hIL-2, hIL-6, hIL-8, hIL-10, hIL-18, and hTNF-$\alpha$. Intra-assay coefficients of variation were 18.5% to 4.6% (n=10), and inter-assay coefficients were 23% to 9% (n=10). The average IL-32 level in the sera of 16 stomach cancer patients (189 pg/ml) was higher than that of 12 healthy control men (109 pg/ml). Our results indicate that serum IL-32 level can be detected by using an established ELISA, and that this immunoassay and mAb KU32-09 specific for immunohistochemistry can be used in the detection of expressed and secreted IL-32 in stomach cancer patients.

• Nutrition Research and Practice
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• 제10권2호
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• pp.131-138
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• 2016

BACKGROUND/OBJECTIVES: Citrus and its peels have been used in Asian folk medicine due to abundant flavonoids and usage of citrus peels, which are byproducts from juice and/or jam processing, may be a good strategy. Therefore, the aim of this study was to examine antioxidant and anti-inflammatory effects of bioconversion of Jeju Hallabong tangor (Citrus kiyomi ${\times}$ ponkan; CKP) peels with cytolase (CKP-C) in RAW 264.7 cells. MATERIALS/METHODS: Glycosides of CKP were converted into aglycosides with cytolase treatment. RAW 264.7 cells were pre-treated with 0, 100, or $200{\mu}g/ml$ of citrus peel extracts for 4 h, followed by stimulation with $1{\mu}g/ml$ lipopolysaccharide (LPS) for 8 h. Cell viability, DPPH radical scavenging activity, nitric oxide (NO), and prostagladin $E_2$ ($PGE_2$) production were examined. Real time-PCR and western immunoblotting assay were performed for detection of mRNA and/or protein expression of pro-inflammatory mediators and cytokines, respectively. RESULTS: HPLC analysis showed that treatment of CKP with cytolase resulted in decreased flavanone rutinoside forms (narirutin and hesperidin) and increased flavanone aglycoside forms (naringenin and hesperetin). DPPH scavenging activities were observed in a dose-dependent manner for all of the citrus peel extracts and CKP-C was more potent than intact CKP. All of the citrus peel extracts decreased NO production by inducible nitric oxide synthase (iNOS) activity and $PGE_2$ production by COX-2. Higher dose of CKP and all CKP-C groups significantly decreased mRNA and protein expression of LPS-stimulated iNOS. Only $200{\mu}g/ml$ of CKP-C markedly decreased mRNA and protein expression of cyclooxygenase-2 in LPS-stimulated RAW 264.7 cells. Both 100 and $200{\mu}g/ml$ of CKP-C notably inhibited mRNA levels of $interleukin-1{\beta}$ ($IL-1{\beta}$) and IL-6, whereas $200{\mu}g/ml$ CKP-C significantly inhibited mRNA levels of $TNF-{\alpha}$. CONCLUSIONS: This result suggests that bioconversion of citrus peels with cytolase may enrich aglycoside flavanones of citrus peels and provide more potent functional food materials for prevention of chronic diseases attributable to oxidation and inflammation by increasing radical scavenging activity and suppressing pro-inflammatory mediators and cytokines.

• Nutrition Research and Practice
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• 제5권3호
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• pp.219-223
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• 2011

Obesity has been reported to be associated with low grade inflammatory status. In this study, we investigated the inflammatory response as well as associated signaling molecules in immune cells from diet-induced obese mice. Four-week-old C57BL mice were fed diets containing 5% fat (control) or 20% fat and 1% cholesterol (HFD) for 24 weeks. Splenocytes ($1{\times}10^7$ cells) were stimulated with $10\;{\mu}g/mL$ of lipopolysaccharide (LPS) for 6 or 24 hrs. Production of interleukin (IL)-$1{\beta}$, IL-6, and TNF-${\alpha}$ as well as protein expression levels of nucleotide-binding oligomerization domain (NOD)2, signal transducer and activator of transcription (STAT)3, and pSTAT3 were determined. Mice fed HFD gained significantly more body weight compared to mice fed control diet ($28.2{\pm}0.6$ g in HFD and $15.4{\pm}0.8$ g in control). After stimulation with LPS for 6 hrs, production of IL-$1{\beta}$ was significantly higher (P=0.001) and production of tumor necrosis factor (TNF)-${\alpha}$ tended to be higher (P < 0.064) in the HFD group. After 24 hrs of LPS stimulation, splenocytes from the HFD group produced significantly higher levels of IL-6 ($10.02{\pm}0.66$ ng/mL in HFD and $7.33{\pm}0.56$ ng/mL in control, P=0.005) and IL-$1{\beta}$ ($121.34{\pm}12.72$ pg/mL in HFD and $49.74{\pm}6.58$ pg/mL in control, P < 0.001). There were no significant differences in the expression levels of STAT3 and pSTAT3 between the HFD and the control groups. However, the expression level of NOD2 protein as determined by Western blot analysis was 60% higher in the HFD group compared with the control group. NOD2 contributes to the induction of inflammation by activation of nuclear factor ${\kappa}B$. These findings suggest that diet-induced obesity is associated with increased inflammatory response of immune cells, and higher expression of NOD2 may contribute to these changes.