• 한방안이비인후피부과학회지
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• 제16권3호
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• pp.82-95
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• 2003

Chemokines are important for the recruitment of leukocytes to sites of infection, which is essential in host defense. The thymus and activation-regulated chemokine (TARC) is a CC chemokine which potentially plays a role via a paracrine mechanism in the development of allergic respiratory diseases. Objectives : The objective of this study is to investigate the effect of Youn-Gyo-Pae-Doc-San on the secretion of TARC of human bronchial epithelial cell Methods : Enzyme-linked immunosorbent assay (ELISA) was performed to detect the secretion of TARC. The cytotoxicity was measured by MTT assay. Results : Youn-Gyo-Pae-Doc-San significantly inhibited the secretion of TARC with a dose -dependant manner. The effective dosage did not have the cytotoxicity on human bronchial epithelial cell. Conclusions : Results of our study show that Youn-Gyo-Pae-Doc-San would play an important role in modulation of TARC in human bronchial epithelial cells.

• Korean Journal of Acupuncture
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• 제22권1호
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• pp.23-32
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• 2005

Chemokines are important for the recruitment of leukocytes, which is essential in host defense to the sites of infection. The thymus and activation-regulated chemokine (TARC) is a CC chemokine which potentially plays a role via a paracrine mechanism in the development of allergic respiratory diseases. Objectives : The objective of this study is to investigate the effect of Ephedrae Herba Herbal Acupuncture Solution(EHS) on the secretion of TARC of human bronchial epithelial cell. Methods : Enzyme-linked immunosorbent assay (ELISA) was performed to detect the secretion of TARC. The cytotoxicity was measured by MTT assay. Results : EHS significantly inhibited the secretion of TARC with a dose-dependant manner. The effective dosage did not have the cytotoxicity on human bronchial epithelial cell. Conclusion : Results of our study imply that EHS would play an important role in modulation of TARC in human bronchial epithelial cells by MTT assay.

• Animal cells and systems
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• 제10권1호
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• pp.15-20
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• 2006

Allergic inflammation is thought to be a Th2 cell-dominant immune response during which tissue-resident fibroblasts produce chemokines which contribute to the recruitment of migratory leukocytes to sites of tissue injury. Thymus and activation-regulated chemokine (TARC; CCL17) is a potent member of the CC chemokine family and a selective chemoattractant for Th2 cells. In order to study the regulatory profiles of TARC production by $TNF-{\alpha}$, $IFN-{\gamma}$, and Il-4 in human normal skin fibroblast, CCD-986sk cell line was used. The expression of TARC protein was measured using ELISA, and mRNA level was detected by RT-PCR. The combination of $TNF-{\alpha}$ and IL-4 induced a time-and dose-dependent synergistic increase in the expression of TARC at both protein and mRNA levels in the cultured human skin fibroblasts. Exposure of the cells to single cytokine had no effect on TARC expression. The high concentration (100 ng/ml) and long incubation time (72 h) of $IFN-{\gamma}$ further enhanced the TARC production induced by $TNF-{\alpha}$/lL-4 in the skin fibroblast. This synergistic effect of Th1 and Th2 type cytokines on TARC production by skin fibroblasts may contribute to the inflammatory cell infiltration and tissue damage with allergic inflammation.

• Journal of Acupuncture Research
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• 제22권1호
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• pp.155-164
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• 2005

사람 기관지 상피세포에 알러지 환경을 유발 하고자 사이토카인을 처리하여 TARC의 분비를 유도하고, 이 케모카인 분비에 반하(半夏) 약쇄액(藥鎖液)이 미치는 효과를 실험한 결과 다음과 같은 결론을 얻었다. 1. 사람의 기관지 상피 세포주에 각각 IL-4, TNF-${\alpha}$, IFN-${\gamma}$ 및 IL-$1{\beta}$를 처리하는 경우와 IL-4와 TNF-${\alpha}$, INF-${\alpha}$와 IFN-${\gamma}$, IFN-${\gamma}$와 IL-$1{\beta}$를 병용 처리할 경우 TARC의 분비량를 측정한 결과 IL-4와 TNF-${\alpha}$와 TNF-${\alpha}$와 IFN-${\gamma}$를 병용 처리하였을 경우 TARC의 분비량이 유의하게 증가하였다. 2. 반하(半夏) 약쇄액(藥鎖液) 처리군의 24시간 및 48시간에서 통계적으로 유의한 감소를 관찰할 수 있었다. 3. 반하(半夏) 약쇄액(藥鎖液)에 의한 TARC 분비억제를 관찰 한 결과 농도의존적인 분비 감소 효과를 관찰 할 수 있었다. 4. MTT assay법을 이용한 세포 독성 측정에선 대조군과 반하(半夏) 약침액(藥鍼液) 처리군간에 유의성이 없었으므로 50, 100 및 200${\mu}g/m{\ell}$의 농도에선 세포독성이 없었음을 관찰할 수 있었다. 이에 반하(半夏) 약광액(藥鑛液)은 TARC 케모카인 억제를 통해 천식에 대한 치료효과를 나타낼 수 있을 것으로 사려된다.

• 동의생리병리학회지
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• 제20권6호
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• pp.1649-1653
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• 2006

Allergic diseases are the result of Th2-dominated responses to single or multiple environmental allergens. Th2 cytokines regulate these mechanisms of allergic disease at many levels, including initiation, progression, and persistence. The effect of hwangryun-Hae-Dok-Tang (HRHDT) on tumor necrosis factor-${\alpha}$ (TNF-${\alpha}$) and interleukin-4 (IL-4) stimulated inflammation was investigated using 3-(4,5-dimethylthiazol-2-yl)-2,5- diphenyltetrazolium bromide assay, thymus and activation-regulated chemokine (TARC), eotaxin, regulated on activation normal T cells expressed and secreted (RANTES) immunoassay on the human bronchial epithelial microglial cells. From the present study, the crude extract of Hwangryun-Hae-Dok-tang suppressed the TNF-${\alpha}$ and IL-4 stimulated TARC, eotaxin, and RANTES production in the human bronchial epithelial A549 cells. Based on the present results, Hwangryun-Hae-Dok-tang may be useful in the treatment asthmatic allergy by inhibiting TARC, eotaxin, and RANTES chemokines.

• Biomolecules & Therapeutics
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• 제21권2호
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• pp.138-145
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• 2013

Citrus fruit contain various flavonoids that have multiple biological activities. However, the content of these flavonoids are changed during maturation and immature Citrus is known to contain larger amounts than mature. Chemokines are significant mediators for cell migration, while thymus and activation-regulated chemokine (TARC/CCL17) and macrophage-derived chemokine (MDC/CCL22) are well known as the typical inflammatory chemokines in atopic dermatitis (AD), a pruritic and chronic inflammatory skin disease. We reported recently that the EtOH extract of immature Citrus unshiu inhibits TARC and MDC production. Therefore, we investigated the activity of flavonoids contained in immature Citrus on TARC and MDC levels. As a result, among the various flavonoids, quercetagetin has stronger inhibitory effects on the protein and mRNA expression of TARC and MDC than other flavonoids. Quercetagetin particularly has better activity on TARC and MDC level than quercetin. In HPLC analysis, the standard peak of quercetagetin matches the peaks of extract of immature C. unshiu. This suggests that quercetagetin is an anti-inflammatory component in immature C. unshiu.

• Natural Product Sciences
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• 제21권3호
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• pp.205-209
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• 2015

Fucoidan, a sulfated polysaccharide is found in several types of edible brown algae. It has shown numerous biological activities; however, the molecular mechanisms on the activity against atopic dermatitis have not been reported yet. We now examined the effects of fucoidan on chemokine production co-induced by TNF-α/IFN-γ, and the possible mechanisms underlying these biological effects. Our data showed that fucoidan inhibited the TNF-α/IFN-γ-induced production of thymus and activation-regulated chemokine (TARC) and macrophagederived chemokine (MDC) mRNA in human keratinocytes HaCaT cells. Also, fucoidan suppressed phosphorylation of nuclear factor kappa B (NF-κB) and activation of signal transducer and activator of transcription (STAT)1 in a dose-dependent manner. In addition, fucoidan significantly inhibited activation of extracellular-signal-regulated kinases (ERK) phosphorylation. These data indicate that fucoidan shows anti-inflammatory effects by suppressing the expression of TNF-α/IFN-γ-induced chemokines by blocking NF-κB, STAT1, and ERK1/2 activation, suggestive of as used as a therapeutic application in inflammatory skin diseases, such as atopic dermatitis.

• 동의생리병리학회지
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• 제21권4호
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• pp.1017-1024
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• 2007

Thymus and activation-regulated chemokine (TARC/CCL-17), produced by keratinocytes, is a CC chemokine known to selectively Th2 type T cells via $CCR4^+$ and is implicated in the development of atopic dermatitis (AD). TARC/CCL17 expression was induced by cytokines such as tumor necrosis factor-${\alpha}$ (TNF-${\alpha}$) and interferon-${\gamma}$ (IFN-${\gamma}$). We recently found that the wogonin, a flavone isolated from Scutellaria baicalensis, suppressed TARC expression via heme oxygenase 1 (HO1) in human keratinocytes induced with mite antigen. However, little is known about the inhibitory mechanism of wogonin on TARC/CCL-17 expression stimulated with cytokines. To investigate the inhibitory mechanism, I determined the inhibitory effects of wogonin on the activation of nuclear factor-${\kappa}B$ (NF-${\kappa}B$) and $I{\kappa}B{\alpha}$ phosphorylation, and also examined the activation of p38 MAP kainase in HaCaT keratinocytes stimulated with TNF-${\alpha}$ and IFN-${\gamma}$. Wogonin inhibited NF-${\kappa}B$-DNA complex, NF-${\kappa}B$ binding activity, and the phosphorylation of $I{\kappa}B{\alpha}$ in a dose dependent manner. Wogonin also inhibited the translocation of NF-${\kappa}B$ from cytosol to nucleus. Moreover, the phosphorylation of of p38 MAP kinase in the TNF-${\alpha}$ and IFN-${\gamma}$-stimulated HaCaT keratinocytes were suppressed by wogonin in a dose dependent manner. These results suggest that wogonin may inhibit cytokine-induced NF-${\kappa}B$ activation by $I{\kappa}B{\alpha}$ degradation via suppression of p38 MAP kinase signaling pathway in keratinocytes and modulation of wogonin signaling pathway may be beneficial for the treatment of AD.

• Toxicological Research
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• 제24권1호
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• pp.17-22
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• 2008

Sopungsan (SS) is a traditional Korean decoction used for the treatment of dermatitis. The aim of this study is to confirm whether or not SS has a preventive effect on the development of atopic dermatitis in dinitrochlorobenzene-applied Nc/Nga mice. SS was administered orally to Nc/Nga mice, which led to the remarkable suppression of the development of dermatitis, as determined by a histological examination and the serum IgE levels. Moreover, SS inhibited the production of thymus- and activation-regulated chemokine (TARC) and its mRNA expression in a keratinocyte cell line, HaCaT, which had been stimulated with tumor necrosis factor-${\alpha}$ (TNF-${\alpha}$) and interferon-${\gamma}$ (IFN-${\gamma}$). Activation of the nuclear factor-${\kappa}B$ (NF-${\kappa}B$) or activator protein-1 (AP-1) is one of key steps in the signaling pathways mediating induction of TARC. In this study, SS selectively suppressed NF-${\kappa}B$ activation which may be essential for TARC expression in $TNF-{\alpha}/IFN-{\gamma}$ treated keratinocytes. The inhibitory effect of SS on NF-${\kappa}B$ activation and TARC production might be associated with the anti-dermatitic effects of SS.

• IMMUNE NETWORK
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• 제2권4호
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• pp.223-226
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• 2002

Background: The type 2 deviated immunological state is predominant in lepromatous leprosy. Erythema nodosum leprosum (ENL) is an immune-complex mediated reaction that typically occurs in lepromatous leprosy. To date, the serum levels of tumor necrosis factor (TNF)-${\alpha}$, interleukin (IL)-2 receptor, IL-10, IL-$1{\beta}$, IL-1 receptor antagonist and monocyte chemoattractant protein-1 (MCP-1) were reported to be higher in lepromatous leprosy. TNF-${\alpha}$ is also known to be higher in ENL, which is reduced after thalidomide treatment. However the serum type 2 chemokine levels in lepromatous leprosy patients have not been reported. Methods: The serum levels of the type 2 chemokines such as thymus and activation-regulated chemokine (TARC), macrophage-derived chemokine (MDC) and eotaxin together with IL-12 and IL-10 in the sera from leprosy patients were detected using an enzyme-linked solvent assay (ELISA) method. Results: The Serum TARC, MDC, eotaxin, IL-10 and IL-12 levels in lepromatous leprosy patients were not significantly different from the normal control levels. The serum levels were not significantly different between the paucibacillary group and multibacillary group. The serum TARC or MDC levels in the ENL patients were more reduced after a treatment containing thalidomide. Conclusion: The type 2 chemokines are not related to the severity of lepromatous leprosy. The larger reducing effect of the TARC or MDC levels in ENL patients by a treatment containing thalidomide suggests the potential role of these chemokines in the development of ENL and the therapeutic mechanism of thalidomide.