• Journal of Periodontal and Implant Science
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• 제23권3호
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• pp.454-460
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• 1993

Abnormalities of the T cell subsets have been detected in the immunologically mediated disease sites such as periodontal lesions which are attributable to the regulatory effect of cell differentiation and specific chemokinetic effect of various cytokines. Macrophage Inflammatory protein$(MIP)-1{\alpha}$ and gammain terferon$({\gamma}-IFN)$ serve as important immunoregulatory molecules through which growth and differentiation of specific T cell subsets are known to be negatively regulated. Murine cytolytic T cell line CTLL-2 were used to perform the [$^3H$]-thymidine incorporation test, by which we obtained more comprehensive view in regulatory actions of cytokines on the T cell subset proliferation. 1. $rMIP-{\alpha}$(200ng/ml) and $r{\gamma}-IFN$(100U/ml) appreared to suppress the proliferation rate to CTLL-2 by 74 and 86% respectively, and the suppressive action of two cytokines were synergisic. 2. Culture supernatant of anti-CD3 mAb-stimulated mouse splenocyte enhanced the proliferation rate of CTLL-2 up to 10-fold with dose-dependent manner. However, culture supernatant of unstimulated splenocyte showed only 2-fold increase in the proliferation rate. 3. CTLL-2 cell proliferation was strictly IL-2 dependent.

• 대한한방소아과학회지
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• 제29권4호
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• pp.39-66
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• 2015

Objectives The purpose of this study is to investigate the effects of Sesamum indicum extracted (SEI) on atopic dermatitis in an in-vitro and in-vivo experiment using a MC/9 murine mast cells and a NC/Nga mouse. Methods In-vitro experiment, IL-4, IL-5, IL-6, IL-13, TNF-${\alpha}$ and GM-CSF mRNA expression were evaluated by Real-time PCR, IL-13, MIP-$1{\alpha}$ production by ELISA and manifestations of NFAT-1, NFAT-2, c-jun, c-fos, NF-${\kappa}B$ p65 transcription factors by western blotting. In-vivo experiment, we measured WBC, Eosinophil, Neutrophil, and serum IL-5, IL-13 in NC/Nga atopic dermatitis mouse, IL-5, IL-13, IFN-${\gamma}$, IL-4 in the spleenocyte culture supernatant by ELISA, the absolute cell numbers of CD4+, CD8+, +Gr-1+CD11b, B220+CD23+ in the axillary lymph node (ALN), peripheral blood mononuclear cells (PBMCs) and dorsal skin tissue, IL-5, IL-13 by Real-time PCR, the distribution of tissue inflammation and cellular infiltration by H&E and toluidine blue. Results SEI decreased IL-4, IL-5, IL-6, IL-13, GM-CSF, TNF-${\alpha}$ mRNA expression, IL-13, MIP-$1{\alpha}$ production and the expression of transcription factors including NFAT-1, c-jun, NF-${\kappa}B$ p65 in MC/9 murine mast cells. SEI orally administration decreased cell number of WBC, Eosinophil, the level of serum IgE, total cell number of ALN and dorsal skin tissue, absolute cell number of CD4+, CD8+, B220+CD23+ in the ALN. SEI orally administration also increased absolute cell number of CD8+/CD3+ and decreased Gr-1+/CD11b+ in PBMCs, decreased CD4+ in dorsal skin tissue, inhibited IL-5, IL-13 mRNA expression. Infiltration levels of inflammatory immune cells, mast cells and thickness of epidermis decreased in dorsal skin tissue. Conclusions SEI can regulate allergic inflammatory response suppressed the gene expression and production of cytokines that mediate allergic reactions, and will be able to be effectively utilized in the treatment of atopic dermatitis future.

• Tuberculosis and Respiratory Diseases
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• 제67권1호
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• pp.14-20
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• 2009

연구배경: 방사선치료 효율의 증가와 방사선 피폭 환자의 치료에 있어 방사선으로 인한 폐 손상의 기전을 잘 파악하는 것이 무엇보다 중요한 일이다. 최근 염증성 cytokine의 활성화가 초기 방사선 폐렴뿐만 아니라 후기에 생기는 폐 섬유화에도 기여하고 있다는 보고들이 많이 나오고 있다. 저자들은 염증성 cytokine의 역할을 알아보기 위하여 방사선 후 흰 쥐의 폐와 혈청에서 이들의 변화를 관찰하였다. 방 법: 90마리의 흰 쥐 폐에 20 Gy의 방사선을 조사한 후 정해진 시간에 폐를 적출하여 병리학적 소견을 관찰하였다. 동시에 혈청과 lung homogenate에서 ELISA kit를 이용하여 염증성 cytokine의 변화를 조사하였다. 결 과: 방사선 조사 후 조직에서 염증세포의 침윤이 증가하고 시간이 지남에 따라 폐 섬유화가 생기는 것을 확인할 수 있었다. TNF-$\alpha$와 IL-1$\beta$는 4시간과 3주째 lung homogenate에서 증가하였는데 3주째 더 많이 증가하는 양상을 보여 주었다. 하지만 혈청에서의 변화는 뚜렷하지 않았다. MIP-2의 경우에는 4시간에 lung homogenate에서만 증가한 반면 HMGB1은 3주째 혈청에서만 증가하는 것을 알 수 있었다. 결 론: 방사선 조사 후 TNF-$\alpha$와 IL-1$\beta$ 등의 염증성 cytokine들이 biphasic expression하는 것을 보여 주었다. 후기 염증성 cytokine들의 증가를 효과적으로 억제할 수 있는 방법이 모색되어야 할 것으로 생각되고 이는 폐 섬유화로 진행하는 만성 합병증을 예방하는 데 기여할 것으로 판단된다.

• 대한한방내과학회지
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• 제38권3호
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• pp.353-366
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• 2017

Objective: This study aimed to use a mouse model to evaluate the effects of Gwaruhaengryeon-hwan (GHH) on chronic obstructive pulmonary disease (COPD) and particulate matter induced lung injury. Materials and Methods: The study was carried out in two ways (in vitro, in vivo). In vitro RAW 264.7 cells (mouse macrophage) were used and analyzed by flow cytometry, ELISA. In vivo lipopolysaccharide (LPS) and cigarette smoke solution (CSS), or coal, fly ash, diesel exhaust particle (CFD) challenged mice were used and its BALF was analyzed by ELISA, lung tissue by real-time PCR. Results: In vitro, GHH maintained an 80-100% rate of viability. So cytotoxicity was not shown. In the ELISA analysis with RAW 264.7 cells, GHH significantly decreased NO over $30{\mu}g/ml$. In the ELISA analysis, GHH significantly decreased $TNF-{\alpha}$, IL-6 over $300{\mu}g/ml$. In the COPD model, the GHH 200 mg/kg dosage group, the application of GHH significantly decreased the increasing of neutrophils, $TNF-{\alpha}$, IL-17A, MIP2, CXCL-1 in BALF, $TNF-{\alpha}$, $IL-1{\beta}$ mRNA expression in lung tissue and histological lung injury. In the CFD induced lung injury model, the GHH 200 mg/kg dosage group, the application of GHH significantly decreased the increase of neutrophils, $TNF-{\alpha}$, IL-17A, MIP2, CXCL-1 in BALF, MUC5AC, $TGF-{\beta}$ mRNA expression in lung tissue and histological lung injury. Conclusion: This study suggests the usability of GHH for COPD patients by controlling lung tissue injury.

• Journal of Ginseng Research
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• 제41권2호
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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.

• 대한한방부인과학회지
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• 제27권1호
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• pp.1-16
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• 2014

Objectives: The purpose of this study was to investigate the effects of Gardeniae Fructus Water Extract (GF) on the production of inflammatory mediators in RAW 264.7 cell treated with lipopolysaccharide (LPS). Methods: Gradeniae Fructus was extracted with distilled water (2,000 ml) for 2 hours. In order to evaluate cytotoxicity of GF, 3 - (4,5-dimethylthiazol-2-yl) - 2,5 - diphenyltetrazolium bromide (MTT) assay was performed. To investigate antiinflammatory effects, the concentration of nitric oxide (NO) was measured with No assay, calcium (Ca) was measured with Fluo-4 Ca assay, and cytokine was measured by Bio-Plex cytokine assay in RAW 264.7 cell. And when p-value is below 0.05, it is judged to have the significant difference statistically. Results: 1. GF did not show any cytotoxicity. 2. GF suppressed the production of NO and Ca at the concentration of 25, 50, 100 and $200{\mu}g/ml$. 3. GF suppressed the production of interleukin (IL)-$1{\beta}$, IL-10, IL-12p40, macrophage-colony stimulating factor (M-CSF), macrophage inflammatory protein (MIP)-$1{\beta}$ and keratinocyte chemoattractant(KC) at the concentration of 25, 50, 100 and $200{\mu}g/ml$. 4. GF suppressed the production of vascular endothelial growth factor (VEGF), granulocyte-colony stimulating factor (G-CSF) and monocyte cheomattractant protein (MCP)-1 at the concentration of 25, 50 and $100{\mu}g/ml$. 5. GF suppressed the production of granulocyte macrophage-colony stimulating factor (GM-CSF) and regulated on activation, normal T cell expressed and secreted (RANTES) at the concentration of 25 and $50{\mu}g/ml$. 6. GF suppressed the production of MIP-2 at the concentration of 50 and $100{\mu}g/ml$, and tumor necrosis factor (TNF)-${\alpha}$ at the concentration of 50 and $200{\mu}g/ml$. Conclusions: These results suggest that GF has anti-inflammatory effect and immuno-modulating activity.

• 대한한의학회지
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• 제39권4호
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• pp.126-135
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• 2018

Objectives: Chronic obstructive pulmonary disease (COPD) is characterized by chronic inflammation and irreversible airflow. This study aimed to evaluate the effects of GHX02 in a COPD-induced mouse model. Methods: The COPD mouse model was established by exposure to cigarette smoke extract and lipopolysaccharide which were administered by intratracheal injection three times with a 7 day interval. GHX02 (100, 200, 400 mg/kg) and all other drugs were orally administrated for 14 days from Day 7 to Day 21. Results: GHX02 significantly decreased the neutrophil counts in bronchoalveolar lavage fluid (BALF) and the number of $CD4^+$, $CD8^+$, $CD69^+$, and $CD11b^+/GR1^+$ cells in BALF and lung cells. GHX02 also suppressed the secretion of tumor necrosis factor-alpha ($TNF-{\alpha}$), interleukin-17A, macrophage inflammatory protein 2 (MIP2), and chemokine (C-X-C motif) ligand 1 (CXCL-1) in BALF and ameliorated the lung pathological changes. Conclusions: Thus, GHX02 effectively inhibited airway inflammation by inhibiting migration of inflammatory cells and expression of pro-inflammatory cytokines. Therefore, GHX02 may be a promising therapeutic agent for COPD.

• 대한의생명과학회지
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• 제18권4호
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• pp.435-437
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• 2012

House dust mite (HDM) is important in the pathogenesis of allergic diseases including asthma and atopic dermatitis. Dermatophagoides pteronissinus (Dp) is one of major HDM allergens. In this study, we investigated that Dp extract (DpE) affects on the chemotactic activity of monocytes isolated from the peripheral blood. DpE inhibited the migration of human monocytes in response to CC chemokines such as MIP-$1{\alpha}$, RANTES, HCC-4, MCP-1, and TARC. DpE did not alter the expression of CC chemokine receptors (CCRs) such as CCR1, CCR2, CCR3, CCR4, and CCR5. These results indicate that DpE blocks the chemotaxis of human monocytes and its mechanism is not involved in alteration of CCR expression. Better understanding of the effect of DpE on monocytes will enable elucidation of the role of Dp in the development of allergic diseases.

• BMB Reports
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• 제46권12호
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• pp.594-599
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• 2013

The anti-inflammatory activity of eriodictyol and its mode of action were investigated. Eriodictyol suppressed tumor necrosis factor (mTNF)-${\alpha}$, inducible nitric oxide synthase (miNOS), interleukin (mIL)-6, macrophage inflammatory protein (mMIP)-1, and mMIP-2 cytokine release in LPS-stimulated macrophages. We found that the anti-inflammatory cascade of eriodictyol is mediated through the Toll-like Receptor (TLR)4/CD14, p38 mitogen-activated protein kinases (MAPK), extracellular-signal-regulated kinase (ERK), Jun-N terminal kinase (JNK), and cyclooxygenase (COX)-2 pathway. Fluorescence quenching and saturation-transfer difference (STD) NMR experiments showed that eriodictyol exhibits good binding affinity to JNK, $8.79{\times}10^5M^{-1}$. Based on a docking study, we propose a model of eriodictyol and JNK binding, in which eriodictyol forms 3 hydrogen bonds with the side chains of Lys55, Met111, and Asp169 in JNK, and in which the hydroxyl groups of the B ring play key roles in binding interactions with JNK. Therefore, eriodictyol may be a potent anti-inflammatory inhibitor of JNK.

• 대한한방내과학회지
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• 제40권4호
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• pp.567-581
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• 2019

Objective: This study aimed to evaluate the inhibitory effects of SGX01 on the lung injuries of COPD mice model. Materials and Methods: This study was carried out in two ways: in vitro and in vivo. In vitro, L929 cells were challenged with LPS, and then treated with six concentrations of SGX01 (10, 30, 50, 100, 300, and $500{\mu}g/ml$) and analyzed by ELISA. In vivo, C57BL/6 mice were challenged with LPS and cigarette smoking solution (CSS), and then treated with a vehicle only (control group), dexamethasone 3 mg/kg (dexa group), or a SGX01 200 mg/kg (SGX01 group). After sacrifice, the BALF or lung tissue was analyzed with Cytospin, FACS, ELISA, real-time PCR and H&E, and Masson's trichrome staining. Results: SGX01 significantly decreased NO, $TNF-{\alpha}$, and IL-6 on L929 cells challenged with LPS. In the COPD model, SGX01 significantly inhibited the increase of neutrophils, $TNF-{\alpha}$, IL-17A, CXCL-1, MIP2, CD8+ cells in BALF, and $TNF-{\alpha}$, $IL-1{\beta}$ mRNA expression in lung tissue. It also decreased the severity of the histological lung injury. Conclusion: This study suggests the usability of SGX01 for COPD patients by controlling lung tissue injury.