• Bulletin of the Korean Chemical Society
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• v.26 no.11
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• pp.1823-1825
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• 2005

Angiogenesis is tightly regulated by a variety of angiogenic activators and inhibitors. Disruption of the balanced angiogenesis leads to the progress of diseases such as cancer, rheumatoid arthritis, and diabetic blindness. Even though a number of proteins involved in angiogenesis have been identified so far, more protein factors remain to be identified due to complexity of the process. Here I report that pituitary tumor-transforming gene (PTTG) induces migration and tube formation of human umbilical vein endothelial cells (HUVECs). High levels of both vascular endothelial growth factor (VEGF) and basic fibroblast growth factor (bFGF) are detected in conditioned medium obtained from cells transfected with PTTG expression plasmid. Taken together, these results suggest that PTTG is an angiogenic factor that induces production of both VEGF and bFGF.

• YAKHAK HOEJI
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• v.51 no.4
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• pp.229-234
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• 2007

We investigated antioxidative activity of the water and ethanol extracts of leaves of Acanthopanax divaricatus var. albeofructus in human dermal fibroblast (HDFs) irradiated by UVA. The irradiation of UVA did not affect the cell viability of HDFs. The antioxidative activity of the extract was investigated by xylenol orange, TBARS (thiobarbituric acid reactive substances) and antioxidant enzyme assay. Both extracts showed H202 scavenging activity and inhibited lipid peroxidation in HDF cells irradiated by UVA. The extracts also recovered enzyme activity in the same cells.

• IMMUNE NETWORK
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• v.12 no.5
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• pp.217-221
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• 2012

Fibroblast-like synoviocytes (FLS) colocalize with leukocyte infiltrates in rheumatoid synovia. Proinflammatory leukocytes are known to amplify inflammation by signaling to FLS, but crosstalk between FLS and regulatory T cells (Tregs) remains uncharacterized. To address this possibility, we cocultured FLS lines derived from arthritic mice with Tregs. FLS that expressed the ligand for glucocorticoid-induced TNF receptor family-related gene (GITR) decreased expression of Foxp3 and GITR in Tregs in a contact-dependent manner. This effect was abolished by blocking antibody to GITR. On the other hand, the Tregs caused the FLS to increase IL-6 production. These results demonstrate that inflamed FLS license Tregs to downregulate Foxp3 expression via the GITRL/GITR interaction while the Tregs induce the FLS to increase their production of IL-6. Our findings suggest that the interaction between FLS and Tregs dampens the anti-inflammatory activity of Tregs and amplifies the proinflammatory activity of FLS, thereby exacerbating inflammatory arthritis.

• Toxicological Research
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• v.16 no.1
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• pp.77-82
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• 2000

This study was conducted to assess a possible alternative method as replacements for in vivo test. The human fibroblasts were exposed to several photoxic chemicals (promethazine, neutral red, chlortetracyclone, amiodatone, bithional, 8-methyooxypsorale) and non-phototoxi substance, ammonium laureth sulfate and irradiatied with 5 J/$cm^2$ of UVA (3320~420nm). The cell viability was measured by NRU (neutral red uptake) assay. The photoxic potential of test chemicals in the NRU PT (phototoxicity test) was assessed by determining the PIF (photoirritancy Factor) by using a cut-off value of 5. The NRU PT responses of most chemicals showed a close agreement with in vivo response except bithinol. There was a relatively good agreement between in vitro NRU assay and in vivo data. These results suggest that NRU assay using fibroblast could be used to predict the phototoxicity.

• Molecular & Cellular Toxicology
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• v.4 no.2
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• pp.150-156
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• 2008

The photoprotective effects of minerals from Korean indigenous ores, consisting mainly of sericite, on UVA-irradiated human dermal fibroblast (HDF) were examined. Zymographic analysis showed that the treatment of the minerals significantly reduced the UVA-enhanced MMP-1 activity and mRNA level. The minerals also showed strong inhibitory effect on MMP-2 activity and mRNA expression. Moreover, the minerals were better than polyphenol in reducing MMP-1 and MMP-2 expressions. Notably, the minerals significantly enhanced collagen biosynthesis in the HDF. Inhibition of the elastase activity and protection against the oxidatively damaged HDF cell were also found in the presence of the minerals. Taken together, the ore minerals may be used as the potent photo-protective and anti-skin-aging ingredients which can prevent skin cell damage by UVA.

• Toxicological Research
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• v.11 no.2
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• pp.229-234
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• 1995

This study was carried out to evaluate the cytotoxicity of cadmium on 3T3 fibroblast and to develop the antidote on 3T3 fibroblast which was injuried by $IC_{50}$ of cadmium. The groups for repaired effects were divided into 7 groups such as medium alone treated group. Cadmium treated $IC_{50}$ groups and 5 experimental groups $(IC_{50}$ cadmium plus $10^{-4}$ concentration of each methanol fraction). After incubation for 48 hrs in the same conditions, MTT (tetrazolium MTT), NR (neutral red) and SRB (sulforhodamine B protein) assay were measured. Light microscopic observations were also investigated. The ethyl acetate fraction of Perilla frutescens showed significantly repaired effect against cadmium cytotoxiclty and this fraction inhibited critical cell regeneration in light microscopy.

• Korean Journal of Environmental Biology
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• v.22 no.1
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• pp.83-88
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• 2004

In order to investigate whether or not CCD-980sk cell line can be affected by Korean Citrus junos and medicinal herbs, we examined the MTT assay when we treated Korean Citrus junos and medicinal herbs in CCD-986sk human fibroblast cell line. The samples that added complex of grinded extracts of Korean Citrus junos and boiling-water extracts from Korean medicinal herbs were tested toy cell proliferation activity by means of a modification of the MTT assay. Among mixture of Citron 3 (Citron 3, less mellowed citron which was ripened for three months) and boiling-water extracts, the group Citron 3+Phellinus linteus showed significantly strong cell proliferation activity. And among mixture of Citron 4 (Citron 4, completely mellowed citron which was ripened for four months) and boiling-water extracts, the group Citron 4＋Cordyceps militaris and Citron 4+Phellinus linteus showed significantly strong cell proliferation activity, respectively. These results suggest that complex of Korean Citrus junos and medicinal herbs could be an excellent candidate toy protection of human skin aging.

• YAKHAK HOEJI
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• v.44 no.2
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• pp.162-168
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• 2000

To investigate the effects of protein kinases on endothelin-1-induced phospholipase C activation and $Ca^{2+}$ mobilization in Rat-2 fibroblast, we measured the formation of inositol phosphates and intracellular $Ca^{2+}$ concentration with [$^3$H]inositol and Fura-2/AM, respectively. Endothelin-1 dose-dependently activated phospholipase C and increased intracellular $Ca^{2+}$ concentration. Protein kinase C activator PMA, significantly inhibited both phospholipase C activity and $Ca^{2+}$ mobilization induced by endothelin-1. Tyrosine kinase inhibitor, genistein, inhibited both. On the other hand, cyclic nucleotide (cAMP and cGMP) did not have any influence on the signaling pathway of phospholipase C-Ca$^{2+}$ mobilization induced by endothelin-1. These results suggest that protein kinase C and tyrosine kinase counteract on the signaling pathway of phospholipase C-Ca$^{2+}$ mobilization induced by endothelin-1 in Rat-2 fibroblast. fibroblast.

• Journal of Periodontal and Implant Science
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• v.29 no.4
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• pp.979-995
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• 1999

This study was investigated to observe the effect of Treponema denticola cell sonicates(TDC) and Treponema lecithinolyticum cell sonicates(TLC) on cytokine secretion and matix metalloproteinase-2(MMP-2) activation of cultured human gingival fibroblast. Several experiments were performed including $IL-1{\beta}$, IL-6 ELISA for the effect on the $IL-1{\beta}$, IL-6 secretion of human gingival fibroblast. Also gelatinase zymography and gelatin dissolubility test for the activation of MMP-2 secreted by gingival fibroblast. The results were as follows. 1. The effect of TDC and TLC on IL-6 secretion of human gingival fibroblast showed statistically significant increase of IL-6 secretion in the TDC and TLC treated group compared to no treatment group(p<0.05) . 2. The amount of $IL-1{\beta}$ secretion was below the lower limit and there was no difference in the $IL-1{\beta}$ secretion of gingival fibroblast between TDC, TLC treated group and no treatment group. 3. The active form of pro MMP-2 with 72 kDa molecular weight was activated in both TDC and TLC treated group and clear band was appeared at 62kDa site on the zymography. 4. Gelatin dissolubility of MMP-2 secreted by gingival fibroblast was higher in TDC and TLC treated group compared to no treatment group(p<0.05). 5. In the TDC treated group, serine protease of T. denticola affect gelatin dissolubility. But in the TLC treated group gelatin was degraded by only MMP secreted by gingival fibroblast. Regarding to the above results, TDC and TLC have an effect on the IL-6 secretion increase of human gingival fibroblast and appears to activate pro MMP-2 which degrades collagen.

• Journal of Physiology & Pathology in Korean Medicine
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• v.22 no.4
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• pp.871-877
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• 2008

Heme oxygenase-1 (HO-1), an inducible heme-degrading enzyme, is expressed by macrophages and endothelial cells in response to various stresses and mediators of inflammation. HO-1 has been recently implicated in regulation of angiogenesis via expression of VEGF. The purpose of this study was to determine the effects of HO-1 modulation on the collagen-induced arthritis (CIA) model and on angiogenesis via up- regulation of VEGF expression in human synovial fibroblast. DBA/1J mice were treated with an inhibitor of HO-1, tin protoporphyrin IX (SnPP), or with an inducer of HO-1, cobalt protoporphyrin IX (CoPP), from day 1 to day 35 after CIA induction. The clinical evolution of disease was monitored visually. At the end of the experiment, histopathologic changes were examined on the joints. VEGF expression in paws were measured by immunohistochemical stain. mRNA expression of HO-1 and VEGF stimulated with various concentration of $TNF-{\alpha}$, CoPP accessed on human synovial fibroblast by RT-PCR. Effects of pretreatment with SnPP on mRNA expression of HO-1 and VEGF in the presence of CoPP and $TNF-{\alpha}$ in synovial fibroblast was accessed by Real-time RT-PCR. Administration of cobalt protoporphyrin IX significantly induced the inflammatory response, with increased arthritis index and expression of VEGF in the paws of the arthritis models. Treatment with SnPP significantly reduced the severity of CIA through inhibition of joint inflammation and cartilage destruction. The expression of VEGF were also significantly reduced by SnPP treatment in the paw. CoPPIX as inducer of HO-1, increased HO-1 and VEGF expression dose dependently in synovial fibroblast. In contrast, inhibition of HO-1 activity by SnPPIX abrogated CoPPIX-induced HO-1 and VEGF production in synovial fibroblast. Stimulation with $TNF-{\alpha}$ increased HO-1 and VEGF expression itself and showed additive effect on HO-1 and VEGF expression when it treated with CoPP. When SnPP was treated with CoPP and $TNF-{\alpha}$, it abrogated the CoPP induced HO-1 and VEGF expression and also abrogated $TNF-{\alpha}$ induced HO-1 and VEGF expression in synovial fibroblast. The effects of HO-1 induction in rheumatoid arthritis results in aggravation of arthritis via up-regulation of VEGF. I concluded that inhibition of the expression or activity of HO-1 could be a therapeutic target of rheumatoid arthritis.