• 한국식품영양과학회지
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• 제43권3호
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• pp.349-354
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• 2014

세포내 $Ca^{{+}{+}}$의 증가는 비만세포에서 수용체 활성을 거치지 않고 탈과립을 유도한다. 괴화는 천연 염색 재료로 사용되고 있으며, 또한 항염증 작용과 $Fc{\varepsilon}RI$와 IgE 가교에 의한 항알레르기 효능도 보고되었다. 이번 연구에서 비만세포에서 $Ca^{{+}{+}}$ 유입에 의해 생산되는 알레르기 매개물에 대한 괴화 추출물의 조절 기능을 보고한다. 괴화 추출물은 A23187에 의해 유도되는 IL-4와 TNF-${\alpha}$의 생산과 탈과립을 저해하였다. 또한 괴화 추출물은 DNFB로 유도한 알레르기 피부염의 동물 모델에서 알레르기 반응을 억제하였다. 괴화추출물 50 mg/kg을 경구투여 또는 도말을 한 경우, DNFB를 단독으로 처리한 군보다 IL-4, TNF 그리고 IFN-${\gamma}$와 같은 염증성 사이토카인의 생산량이 감소하였다. 또한 괴화 추출물을 처리한 경우 혈청 내 IgE의 함량이 DNFB를 단독으로 처리한 군보다 감소하였다. 괴화 추출물을 처리한 군에서의 비장과 림프절의 무게도 DNFB를 단독으로 처리한 군보다 감소하였다. 이러한 결과를 토대로 괴화는 비만세포에서 $Fc{\varepsilon}RI$ 자극뿐만 아니라 $Ca^{{+}{+}}$의 유입에 의한 항알레르기 효능이 있다는 것을 보고한다.

• 대한한방소아과학회지
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• 제25권1호
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• pp.1-27
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• 2011

Objectives: The purpose of this study is to investigate the effects of Yijungtang(YJT) on atopic dermatitis in an in-vitro and in-vivo experiment using a RBL-2H3 mast cells and a NC/Nga atopic dermatitis mouse. Methods: In-vitro experiment, IL-4, IL-13 mRNA expression were evaluated by a real-time PCR, IL-4, IL-13 production by ELISA and transcription factor as GATA-1, GATA-2, NF-AT1, NF-AT2, AP-1 and NF-kB by western blotting. In-vivo experiment, clinical skin score we evaluated by, hematology and Serum total IgE and IgG1 of NC/Nga atopic dermatitis mouse, cytokine level, total number of cell, Immunohistochemical staining and Histological features of auxiliary lymph node(ALN), draining lymph node(DLN), peripheral blood mononuclear cells(PBMCs) and dorsal skin tissue in NC/Nga mouse. Results: YJT decreased IL-4, IL-13 mRNA expression, IL-4, IL-13 production and prominently decreased the expression of mast cell specific transcription factors including GATA-2, NF-AT2, c-Fos and NF-kB. YJT oral administration reduced the levels of skin severity scores. It also decreased the level of inflammatory cytokines such as IL-5, IL-13, histamine and IgE in the serum. It elevated IFN-gamma level in the spleenocyte culture supernatant but decreased. $CD3e^+$, $CD19^+$, $CD4^+$, $CD8^+$, $CD3e^+CD69^+$, $CD11b^+Gr-1^+$, $CCR3^+$ in the PBMCs, $CD4^+$, $CD8^+$, $CD3e^+CD69^+$, $B220^+CD23^+$ in the ALN, $CD4^+$, $CD3e^+CD69^+$ in the ALN and $CD4^+$, $CD11b^+Gr-1^+$ in the dorsal skin. Histological examination showed that infiltration levels of immune cells in the skin of AD-induced NC/Nga mice were much improved by YJT oral administration. Conclusions: The anti-allergic activities of YJT may be mediated by down-regulation of Th2 cytokines, such as IL-4 and IL-13, through the regulation GATA-2, NF-AT2 and NF-kB transcription factors in mast cells. YJT would be regulate molecular mediators and immune cells which are functionally associated with atopic dermatitis induced in NC/Nga mice, and may play an important role in recovering AD symptoms.

• Journal of Chest Surgery
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• 제35권2호
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• pp.118-126
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• 2002

배경: 체외순환에 의해 생성되는 염증매개체는 소아 환자에서 술 후 다기관 기능부전과 연관이 있다. 본 연구에서는 선천성 신장질환 소아환자에서 체외순환에 의한 전염증성 사이토카인과 케모카인의 유전자 발현 특성에 대해 알아보고자 하였다. 대상 및 방법: 개심술을 시행한 18명의 소아 환자의 요골 동맥에서 마취유도 후(기준치), 체외순환(0시간), 체외순환 2시간 후 24시간 후, 48시간 후에 혈액을 채취하였다. 모든 환자에서 인터루킨-1알파, 인터루킨-1베타 인터루킨-6, 인터루킨-8, 종양괴사자인자-알파, 인터루킨-15,인터페론 감마의 mRNA의 유전자 발현 정도를 반정량적으로 역전사 중합효소 연쇄반응으로 측정하였다. 6명의 환자에서 인터루킨-6단백치는효소결합면역흡착검사로 측정하였다. 결과: 전신적인 인터루킨-6 mRNA와 비슷한 양상을 보였으나 최고치는 인터루킨-6보다 낮은 값을 보였다. 인터루킨-1알파와 인터루킨-1베타의 mRNA의 발현은 체외순환 2시간 후에 최고치를 나타내었고 체외순환 2시간 후에 최고치를 나타내었고 체외순환 48시간 후에 감소하였다. 종양괴사자인자-알파는 체외 순환 24시간 후에 최고치를 나타내었고 체외순환 48시간 후에 감소하였다. 인터루킨-15 mRNA 발현은 체외순환 전후와 비교하여 유의한 변화가 없었다. 인터페론-감마는 시간이 지남에 따라 감소하였다. 결론: 선천성 심장질환으로 개심술을 시행한 소아환자의 혈청 내 인터루킨-6, 인터루킨-8, 인터루킨-1알파, 인터루킨-베타, 종양괴사자인자-알파의 유전자 발현은 체외 순환 전후로 유의한 변화를 보였다. 인터루킨-15는 유의한 변화가 없었고 인터페론-감마는 반대 양상의 변화를 보였다. 체외순환 후 전염증성 사이토카인과 케모카인의 높은 혈중 농도는 술 후 조직 손상과 연관되리라 생각한다.

• 생명과학회지
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• 제23권8호
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• pp.1057-1063
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• 2013

진피(Citri Pericarpium)의 항암작용 기전 해석을 위하여 U937 백혈병 세포의 apoptosis 유발에 미치는 메탄올 추출물(EMCP)의 영향을 조사하였으며, apoptosis 조절에 중요한 몇 가지 유전자들의 발현 및 활성 변화, ROS의 생성 변화를 조사하였다. EMCP 처리에 의한 U937 세포의 증식 억제는 apoptosis 유도와 연관성이 있음을 DAPI 염색을 통한 apoptotic body 출현의 증가 및 Flow cytometry 분석에 의한 Sub-G1기 세포 빈도의 증가로 확인하였다. EMCP 처리에 의한 apoptosis 유도에서 Bax 발현 증가, caspases의 활성 및 PARP의 단편화 등이 동반되었으며, ROS 생성의 증가와 연관성이 있었다. 산화적 손상에 대해 세포나 조직을 보호하는 역할을 하는 것으로 알려진 세포 내 항산화 효소인 HO-1의 발현이 EMCP의 처리에 의해 증가되었으나 ROS 생성 억제제인 NAC의 전처리에 의해 감소된 HO-1의 발현은 전사인자인 Nrf2의 핵으로의 이동 억제와 관련되어 있었다. 이상의 결과에서 EMCP 처리에 의한 U937 세포의 apoptosis 유발에는 ROS 생성의 증가와 pNrf2에 의해 조절되는 HO-1의 발현 증가가 중요한 기전으로 작용한다는 것을 알 수 있었다. 이러한 자료는 진피의 항암기전 해석을 이해하는데 중요한 기초자료로서 활용될 수 있을 것으로 생각된다.

• Journal of Nutrition and Health
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• 제49권6호
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• pp.429-436
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• 2016

본 연구에서는 피부의 표피와 진피에 분포하는 HaCaT 세포와 HDF 세포를 이용하여 항산화효과가 우수한 두릅순 추출물의 처리가 UVB에 의한 피부광노화를 억제할 수 있는지 알아보기 위하여 피부 염증반응과 관련한 사이토카인과 피부의 주요 구성 단백질인 collagen에 영향을 미칠 수 있는 MMP-1, type-I procollagen, TRPV-1 등의 단백질 발현에 미치는 영향을 분석하였다. HaCaT에 두릅순 추출물을 24시간 전처리한 경우 UVB ($55 mJ/cm^2$) 노출로 인해 증가한 염증매개인자인 IL-6, IL-8, $PGE_2$를 유의하게 감소시켰다. 또한, 피부 collagen의 정상적인 구조 및 양에 영향을 미치는 단백질들의 발현을 측정한 결과 HaCaT에서는 UVB 조사로 인해 증가한 TRPV-1과 MMP-1 단백질의 발현이 두릅순 에탄올 추출물의 전처리로 모두 감소하였고, HDF에서는 UVB를 조사한 대조군에 비하여 두릅순 추출물 처리가 MMP-1 단백질 발현을 감소시키는 동시에 collagen의 전구체인 type-I procollagen의 발현을 증가시키는 효과를 보였다. 이들 결과들로부터 항산화효과가 우수한 두릅순 70% 에탄올 추출물은 피부세포에서 UVB에 의한 염증반응을 억제시키는 동시에 피부 collagen의 감소를 억제시킴으로써 피부 광노화를 예방할 수 있는 천연 소재로 이용될 수 있다고 본다.

• The Korean Journal of Physiology and Pharmacology
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• 제2권4호
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• pp.521-527
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• 1998

An important property of the intestine is the ability to secrete fluid. The intestinal secretion is regulated by a number of substances including vasoactive intestinal peptide (VIP), ATP and different inflammatory mediators. One of the most important secretagogues is adenosine during inflammation. However, the controversy concerning the underlying mechanism of adenosine-stimulated $Cl^-$ secretion in intestinal epithelial cells still continues. To investigate the effect of adenosine on $Cl^-$ secretion and its underlying mechanism in the rabbit colon mucosa, we measured short circuit current ($I_{SC}$) under automatic voltage clamp with DVC-1000 in a modified Ussing chamber. Adenosine, when added to the basolateral side of the muocsa, increased $I_{SC}$ in a dose-dependent manner. The adenosine-stimulated $I_{SC}$ response was abolished when $Cl^-$ in the bath solution was replaced completely with gluconate. In addition, the $I_{SC}$ response was inhibited by a basolateral Na-K-Cl cotransporter blocker, bumetanide, and by apical $Cl^-$ channel blockers, dephenylamine-2-carboxylate (DPC), 5-nitro-2-(3-phenyl-propylamino)-benzoate (NPPB), glibenclamide. Amiloride, an epithelial $Na^+$ channel blocker, and 4,4-diisothiocyanato-stilbene-2,2-disulphonate (DIDS), a $Ca^{2+}-activated$ $Cl^-$ channel blocker, had no effect. In the mucosa pre-stimulated with forskolin, adenosine did not show any additive effect, whereas carbachol resulted in a synergistic potentiation of the $I_{SC}$ response. The adenosine response was inhibited by 10 ${\mu}M$ H-89, an inhibitor of protein kinase A. These results suggest that the adenosine-stimulated $I_{SC}$ response is mediated by basolateral to apical $Cl^-$ secretion through a cAMP-dependent $Cl^-$ channel. The rank order of potencies of adenosine receptor agonists was $5'-(N-ethylcarboxamino)adenosine(NECA)＞N^6-(R-phenylisopropyl)adenosine(R-$ PIA)＞2-[p-(2-carbonylethyl)-phenyl-ethylamino]-5'-N-ethylcarboxaminoadenosine(CGS21680). From the above results, it can be concluded that adenosine interacts with the $A_{2b}$ adenosine receptor in the rabbit colon mucosa and a cAMP-dependent signalling mechanism underlies the stimulation of $Cl^-$ secretion.

• Journal of Periodontal and Implant Science
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• 제35권4호
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• pp.1053-1071
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• 2005

To find out the suppressive effect of natural extract Curcuma xanthorrhiza on $IL-1{\beta}$ and MMP-2 derived from periodontal ligament cells through in vitro study and to confirm its effect on plaque and gingivitis through clinical study, Curcuma xanthorrhiza containing toothpaste was used and following results were produced. 1. In vitro study, type IV collagenase MMP-2 production was inhibited dose-dependently in the group treated with Curcuma xanthorrhiza compared to the control group. 2. In vitro study, the production of $IL-l{\beta}$ which is one of the inflammatory mediators associated with periodontitis was inhibited dose-dependently in the group treated with Curcuma xanthorrhiza. 3. On the third week, the plaque index of the groups treated with or without Curcuma xanthorrhiza containing toothpastes were both increased significantly compared to the baseline(p<0.05). 4. On the third week, the gingival index of the group treated with Curcuma xanthorrhiza containing toothpaste was not significantly different from baseline. However, the group treated without Curcuma xanthorrhiza containing toothpaste showed a significant increase of gingival index at shielded area(p<0.05). 5. The gingival index of the group without Curcuma xanthorrhiza containing toothpaste showed a significant increase in the sites without tooth brushing when compared to sites with tooth brushing(p<0.05). However. there was no significant difference for the group with Curcuma xanthorrhiza containing toothpaste in sites either with or without tooth brushing. 6. The Bleeding on probing for the group without Curcuma xanthorrhiza containing toothpaste showed no significant difference even when tooth brushing was done. However, for the group with Curcuma xanthorrhiza containing toothpaste, bleeding on probing was significantly reduced compared to baseline when tooth brushing was done(p<0.05).

• Journal of Periodontal and Implant Science
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• 제37권4호
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• pp.743-753
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• 2007

Purpose: The purposes of this study were to compare and quantify the expression of MMP-3, $PGE_2$ and IL-6 in the gingival tissues of patients with $type_2$ diabetes mellitus and healthy adults with chronic periodontitis. Material and methods: Gingival tissue samples were obtained during periodontal surgery or tooth extraction. According to the patient's systemic condition & clinical criteria of gingiva, each gingival sample was devided into three groups. Group 1(n=8) is clinically healthy gingiva without bleeding and no evidence of bone resorption or periodontal pockets, obtained from systemically healthy 8 patients. Group 2(n=8) is inflamed gingiva from patients with chronic periodontitis. Group 3(n=8) is inflamed gingiva from patients with chronic periodontitis associated with type 2 DM. Tissue samples were prepared and analyzed by Westernblotting. The quantification of MMP-3, $PGE_2$ and IL-6 were performed using a densitometer and statistically analyzed by one-way ANOVA followed by Tukey test. Results: 1. The expression levels of MMP-3 were shown highest in group 3 compared to group 1 and 2, and It showed increasing tendency in group 2 and 3. 2. The expressions of $PGE_2$ and IL-6 were shown increasing tendency in group 2 and 3, and It was highest in group 3. 3. As expressions of MMP-3 were increased, $PGE_2$ and IL-6 expressions showed increasing tendency in group 3 than group1 and 2, although there were no proportional relationship. Conclusion: This study demonstrated that the expression levels of MMP-3, $PGE_2$ and IL-6 will be inflammatory markers of periodonta linflamed tissue and DM. It can be assumed that MMP-3 affect to expressions of $PGE_2$ and IL-6 in progression of periodontal inflammation with alveolar bone resorption to type 2 DM.

• Archives of Pharmacal Research
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• 제25권2호
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• pp.170-177
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• 2002

The herb, Chrysanthemum zawadskii var, latilobum commonly known as Gu-Jul-Cho in Korea, used in traditional medicine to treat pneumonia, bronchitis, cough, common cold, pharyngitis, bladder-related disorders, gastroenteric disorders, and hypertension. Linarin is the main active compound and the biological mechanisms of its activity are unclear. It is believed that effects of this herb may be exerted through the pluripotent effectors of linarin due to its ability to treat a variety of afflictions. In this study, the effects of linarin on the mouse macrophages cell line, RAW 264.7, were investigated. It was found that linarin could activate macrophages by producing cytokines. Monocytes and tissue macrophages produce at least two groups of protein mediators of inflammation, interleukin 1 (IL-1 ) and the tumor necrosis factor (TNF). Recent studies have shown that TNF and IL-1 modulate the inflammatory function of endothelial cells, leukocytes, and fibroblasts. $TNF-{\alpha}$ production by macrophages treated with linarin occured in a dose dependent manner However, IL-1 production was largely unaffected by this natural product. This study demonstrated the ability of linarin to activate macrophages both directly and indirectly. Linarin also affect both cytosine production and nitric oxide inhibition, in addition to the expression of some surface molecules. Nitric oxide (NO), derived from L-argin-ine, is produced by two forms(constitutive and inducible) of nitric oxide synthase (NOS). The NO produced in large amounts by inducible NOS is known to be responsible for the vasodilation and hypotension observed in septic shock. Linarin was found to inhibit NO production in the LPS-activated RAW 264.7 cells. Linarin may be a useful candidate as a new drug for treating endotoxemia and the inflammation accompanied by NO overproduction. The linarin-treated total Iymphocytes exhibited cytotoxicity in a dose dependent manner between $20{\;}{\mu}g/ml{\;}and{\;}40{\;}{\mu}g/ml$. These results suggest that linarin may function through macrophage activation.

• The Korean Journal of Physiology and Pharmacology
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• 제16권6호
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• pp.393-398
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• 2012

Mast cells are involved in allergic responses, protection against pathogens and autoimmune diseases. Dexamethasone (Dex) and other glucocorticoids suppress $Fc{\varepsilon}RI$-mediated release of inflammatory mediators from mast cells. The inhibition mechanisms were mainly investigated on the downstream signaling of Fc receptor activations. Here, we addressed the effects of Dex on Fc receptor expressions in rat mast cell line RBL-2H3. We measured mRNA levels of Fc receptors by real-time PCR. As expected, Dex decreased the mRNA levels of activating Fc receptor for IgE ($Fc{\varepsilon}R$) I and increased the mRNA levels of the inhibitory Fc receptor for IgG $Fc{\gamma}RIIb$. Interestingly, Dex stimulated transcriptions of other activating receptors such as Fc receptors for IgG ($Fc{\gamma}R$) I and $Fc{\gamma}RIII$. To investigate the mechanisms underlying transcriptional regulation, we employed a transcription inhibitor actinomycin D and a translation inhibitor cycloheximide. The inhibition of protein synthesis without Dex treatment enhanced $Fc{\gamma}RI$ and $Fc{\gamma}RIII$ mRNA levels potently, while $Fc{\varepsilon}RI$ and $Fc{\gamma}RIIb$ were minimally affected. Next, we examined expressions of the Fc receptors on cell surfaces by the flow cytometric method. Only $Fc{\gamma}RIIb$ protein expression was significantly enhanced by Dex treatment, while $Fc{\gamma}RI$, $Fc{\gamma}RIII$ and $Fc{\varepsilon}RI$ expression levels were marginally changed. Our data showed, for the first time, that Dex regulates Fc receptor expressions resulting in augmentation of the inhibitory receptor $Fc{\gamma}RIIb$.