• Tuberculosis and Respiratory Diseases
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• 제48권2호
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• pp.223-235
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• 2000

배 경: 액체환기가 손상된 폐에 긍정적인 영향을 주는 한 기전으로 perfluorocarbon(PFC)이 기도상피세포에서 chemokine발현을 억제할 수 있는 지를 관찰하기 위해 본 연구를 시행하였다. 방 법: 기도 상피세포로는 A549 세포주를, PFC로는 perfluorodecalin을, PFC의 노출은 Transwell$^{(R)}$배양접시의 lower chamber를 이용하여 시행하였다. PFC가 말초혈액 탄핵구층(peripheral blood mononuclear cell : PBMC)의 기능을 억제해서 A549세포의 chemokine 발현을 억제할 수 있는지를 관찰하기 위해서 PBMC를 분리하여 Transwell$^{(R)}$ 접시에서 배양하면서 lipopolysaccharide(LPS, 10 ${\mu}g/mL$)로 자극과 PFC의 노출에 따라 군을 나누었으며 24시간 후 그 배양 상층액을 포함한 conditioned media(CM)으로 24시간 동안 A549세포를 자극한 후 chemokine발현을 측정하였다. 또한 PFC가 직접 기도 상피세포의 기능을 억제할 수 있는 지를 관찰하기 위해서 A549 세포를 Transwell$^{(R)}$ 접시에서 배양하면서 interleukin-l$\beta$(IL-1$\beta$, 10 ng/ml), TNF-$\alpha$(10 ng/ml)로 각각 혹은 동시에 24시간동안 자극하면서 PFC노출여부에 따른 IL-8과 RANTES발현 정도를 비교하였다. Chemokine 발현은 IL-8과 RANTES의 단백에 대한 ELISA와 mRNA는 Northern analysis를 통하여 분석하였다. 결 과: 1. LPS로 자극한 PBMC의 배양상층액을 포함한 CM로 A549세포를 자극하였을 때 IL-8과 RNATES mRNA 발현과 면역반응성 단백 생성이 의미 있게 상승하였으나(p<0.05) PFC노출여부에 따른 유의한 차이는 관찰할 수 없었다. 2. TNF-$\alpha$와 IL-1$\beta$ 모두 A549세포에서 IL-8과 RANTES mRNA자발현과 면역반응성 단백 생성의 증가를 가져왔으나(p<0.05) PFC노출에 따른 유의한 차이는 관찰할 수 없었다. 결 론: 기도 상피세포의 chemokine발현 감소를 통한 항염증 작용은 액체환기시 보이는 염증반응 감소에 큰 기여를 하지 않을 것으로 생각되며 추후 액체환기시 관찰되는 염증반응의 감소의 기전에 대한 연구가 더 필요할 것으로 사료된다.

• Journal of Microbiology and Biotechnology
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• 제14권4호
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• pp.722-729
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• 2004

Leptin is an adipocyte-secreted hormone and its plasma levels correlate with total body fat mass, however, it also plays a regulatory role in immunity, inflammation, and hematopoiesis. Chemokine is known as a chemoattractant cytokine in inflammatory reaction, but its role in leptin reaction has not been well studied. In this study, the direct effect of leptin on the expression of chemokine mRNAs and lipopolysaccharide (LPS)-induced chemokine KC mRNA in mouse peritoneal macrophages was investigated. Leptin did not induce the expression of lymphotactin, RANTES, eotaxin, MIP-1$\beta$, MIP-1$\alpha$, MIP-2, MCP-1, IP-10, TCA-3, and KC mRNA in mouse peritoneal macrophages, and had no direct effect on the expression of these LPS-induced chemokine mRNAs except KC mRNA. The synergistic effect of leptin on the expression of LPS-induced KC mRNA occurred late in the time course of response to LPS. The increased expressions of Ob-Rb mRNA and leptin receptor protein were detected during the LPS treatment. Leptin produced a substantial increase in the stability of the LPS-induced KC mRNA, and the synergistic effect of leptin on LPS-induced KC mRNA expression was further augmented by cycloheximide (CHX). Pyrrolidine dithiocarbamate (PDTC) did not block the synergistic effect of leptin on LPS-induced KC mRNA expression in mouse peritoneal macrophages. These data suggest that although leptin has no direct effect on the expression of lymphotactin, RANTES, eotaxin, MIP-1$\beta$, MIP-1$\alpha$, MIP-2, MCP-1, IP-10, TCA-3, and KC mRNA in mouse peritoneal macrophages, the synergistic effect of leptin on the expression of LPS-induced KC mRNA has the possibility that LPS might induce the expression of the Ob-Rb receptor or an unknown gene(s) that sensitizes macrophages to the synergistic function of leptin. Therefore, further studies are necessary to examine leptin as a regulatory factor of chemokine production.

• 통합자연과학논문집
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• 제8권3호
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• pp.164-175
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• 2015

CXCR3 is a C-X-C chemokine receptor type 3 also known as GPR9 and CD183. CXCR3 is a G-Protein coupled chemokine receptor which interacts with three endogenous interferon inducible chemokine's (CXCL9, CXCL10 and CXCL11) and is proved to play a vital role in the Th1 inflammatory responses. CXCR3 has been implicated to be associated with various disease conditions like inflammatory diseases, autoimmune diseases, type I diabetes and acute cardiac allograft rejection. Therefore CXCR3 receptor is found to be an attractive therapeutic target for the treatment of inflammatory diseases. Inorder to decipher the biological function of a CXCR3, 3D structure is of much important but the crystal structure for CXCR3 has not yet been resolved. Hence, in the current study Homology modeling of CXCR3 was performed against various templates and validated using different parameters to suggest the best model for CXCR3. The reported best model can be used for further studies such as docking to identify the important binding site residues.

• 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.

• 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.

• Molecules and Cells
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• 제43권11호
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• pp.921-934
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• 2020

Lck-interacting transmembrane adaptor 1 (LIME) has been previously identified as a raft-associated transmembrane protein expressed predominantly in T and B lymphocytes. Although LIME is shown to transduce the immunoreceptor signaling and immunological synapse formation via its tyrosine phosphorylation by Lck, a Src-family kinase, the in vivo function of LIME has remained elusive in the previous studies. Here we report that LIME is preferentially expressed in effector T cells and mediates chemokine-mediated T cell migration. Interestingly, in LIME^-/- mice, while T cell receptor stimulation-dependent proliferation, differentiation to effector T cells, cytotoxic T lymphocyte (CTL) function and regulatory T lymphocyte (Treg) function were normal, only T cell-mediated inflammatory response was significantly defective. The reduced inflammation was accompanied by the impaired infiltration of leukocytes and T cells to the inflammatory sites of LIME^-/- mice. More specifically, the absence of LIME in effector T cells resulted in the reduced migration and defective morphological polarization in response to inflammatory chemokines such as CCL5 and CXCL10. Consistently, LIME^-/- effector T cells were found to be defective in chemokine-mediated activation of Rac1 and Rap1, and dysregulated phosphorylation of Pyk2 and Cas. Taken together, the present findings show that LIME is a critical regulator of inflammatory chemokine-mediated signaling and the subsequent migration of effector T cells to inflammatory sites.

• Journal of Acupuncture Research
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• 제20권4호
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• pp.53-65
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• 2003

Although the effect of Bee Venom has been reported, its mechanism has not been fully elucidated. Nitric Oxide(NO) is one of the free radicals and mediates in inflammation diseases. Chemokines contribute to the pathogenesis of several disorders such as allergic rhinitis and rheumatoid arthritis and so on. The objective of this study was to investigate the scavenging effect of Bee Venom on NO and on expression of chemokine genes. There was no significant NO scavenging effect in Crude Bee Venom, Apamin, Melittin, and MCD-peptide. The expression of chemokines was examined by RT-PCR using the human mast cell line(HMC-1), which is known to secrete and express chemokines. In order to investigate the protective effect of Bee Venom, HMC-1 cells were incubated with pretreatment of Bee Venom for 24 hrs and stimulated with 1 uM calcium ionophore A23178 for 2 hrs. RT-PCR analyses of chemokine genes showed that expressions of RANTES and MCP-1 were increased compared to the calcium ionophore-only treated group. But IL-8 and MCP-3 did not express increasing effect compared to control group. This study may provide important basic data on the possibility of the clinical treatment of Bee Venom in inflammation diseases.

• Asian Pacific Journal of Cancer Prevention
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• 제15권17호
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• pp.7201-7205
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• 2014

Chemokine and chemokine receptor expression by tumor cells contributes to tumor growth and angiogenesis and thus these factors may be considered as tumor markers. Here we aimed to characterize cells directly extracted from glioma, meningioma, and secondary brain tumors as well as non-tumoral cells in vitro. Cells were isolated from brain tissues using 0.2% collagenase and characterized by flow cytometry. Expression of SDF-1, CXCR4, CXCR7, RANTES, CCR5, MCP-1 and IP-10 was defined using flow cytometry and qRT-PCR methods. Brain tissue isolated cells were observed as spindle-shaped cell populations. No significant differences were observed for expression of SDF-1, CXCR4, CXCR7, RANTES, CCR5, and IP-10 transcripts. However, the expression of CXCR4 was approximately 13-fold and 110-fold higher than its counterpart, CXCR7, in meningioma and glioma cells, respectively. CXCR7 was not detectable in secondary tumors but CXCR4 was expressed. In non tumoral cells, CXCR7 had 1.3-fold higher mRNA expression than CXCR4. Flow cytometry analyses of RANTES, MCP-1, IP-10, CCR5 and CXCR4 expression showed no significant difference between low and high grade gliomas. Differential expression of CXCR4 and CXCR7 in brain tumors derived cells compared to non-tumoral samples may have crucial impacts on therapeutic interventions targeting the SDF-1/CXCR4/CXCR7 axis.

• 대한본초학회지
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• 제37권3호
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• pp.41-47
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• 2022

Objectives : Terminalia chebula (TC) has been used as a traditional remedy to treat gastrointestinal infectious and inflammatory diseases. However, its protective effects and mechanisms against skin inflammation have not been well-elucidated. Thus, the aim of this study is to evaluate the protective effects of the TC water extract and also to suggest a putative mechanism of TC against skin injury on human keratinocytes, HaCaT cells. Methods : HaCaT cells were pre-treated with TC for 1 h and then stimulated with tumor necrosis factor-alpha (TNF-α) and interferon-gamma (IFN-γ) (10 ng/mL each) to induce skin inflammation and injury. After 24 h, the cells were harvested to evaluate the expression of Th2 chemokines, such as C-C motif chemokine ligand 5 (CCL5, also known as RANTES), C-C chemokine ligand 17 (CCL17, also known as TARC) and C-C chemokine ligand 22 (CCL22, also known as MDC). To investigate the regulatory mechanisms of TC, we also assessed the phosphorylation of signal transducer and activator of transcription 1 (STAT1) signaling pathways in HaCaT cells. Results : Treatment of TC decreased the mRNA levels of RANTES, TARC and MDC with a concentration dependent manner against co-stimulation of TNF-α and IFN-γ. In addition, TC significantly reduced TNF-α and IFN-γ induced phosphorylation of STAT1. Conclusions : In summary, we propose that TC may be a promising candidate for anti-inflammatory skin protector through the inhibition of chemokines via STAT1 deactivation.