• Title/Summary/Keyword: Fibroblast activation

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Evaluation of the Genetic Toxicity of Synthetic Chemicals (III) - in vitro Chromosomal Aberration Assay with 28 Chemicals in Chinese Hamster Lung Cells -

  • Ryu, Jae-Chun;Kim, Kyung-Ran;Lee, Soo-Young;Park, Jong-Sei
    • Environmental Mutagens and Carcinogens
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    • v.21 no.1
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    • pp.14-22
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    • 2001
  • The detection of many synthetic chemicals used in industry that may pose a genetic hazard in our environment is of great concern at present. In this respect, administrative authorities has great concern to regulate and to evaluate the chemical hazard to environment and human health. The clastogenicity of 28 synthetic chemicals was evaluated in Chinese hamster lung fibroblast cells in vitro. Glycidylacrylate which is one of the most cytotoxic chemical among 28 chemicals tested revealed clastogenicity in the range of 0.31-1.25 $\mu\textrm{g}$/$m\ell$ both in the presence and absence of metabolic activation system. Neopentyl glycol (340-1360 $\mu\textrm{g}$/$m\ell$) also revealed weak positive result both in the presence and absence of metabolic activation system. Cyanoguanidine (/$420.5-841 $\mu\textrm{g}$m\ell$) and N-butylchloride ($231.5-926 $\mu\textrm{g}$/m\ell$) revealed weak positive result only in the absence of S-9 metabolic activation system. Nevertheless total aberration percentages of N-butylchloride in the presence of metabolic activation system, and 3,4'-dichlorobenztrifluoride in the absence of S-9 metabolic activation revealed above 5% aberration, there is no statistical significance. From the results of chromosomal aberration assay with 28 synthetic chemicals in Chinese hamster lung cells, glycidylacrylate (CAS No. 106-90-0), neopentyl glycol (CAS No. 126-30-7), N-butyl chloride (CAS No. 109-69-3) and cyanoguanidine (CAS No. 461-58-5) revealed positive clastogenic results in this study.

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The Effect of Sonicated Extracts of Treponema Denticola and Treponema Lecithinolyticum on the Cytokine Secretion and Matrix Metalloproteinase Activation of Gingival Fibroblast (Treponema denticola와 Treponema lecithinolyticum의 분쇄액이 치은섬유아세포의 Cytokine 분비 및 Matrix metalloproteinase 활성에 미치는 영향)

  • Suh, Hye-Yuhn;Choi, Bong-Kyu;Choi, Seong-Ho;Cho, Kyoo-Sung;Kim, Chong-Kwan;Chai, Jung-Kiu
    • 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.

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Renal fibrosis

  • Cho, Min-Hyun
    • Clinical and Experimental Pediatrics
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    • v.53 no.7
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    • pp.735-740
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    • 2010
  • Renal fibrosis, characterized by tubulointerstitial fibrosis and glomerulosclerosis, is the final manifestation of chronic kidney disease. Renal fibrosis is characterized by an excessive accumulation and deposition of extracellular matrix components. This pathologic result usually originates from both underlying complicated cellular activities such as epithelial-to-mesenchymal transition, fibroblast activation, monocyte/macrophage infiltration, and cellular apoptosis and the activation of signaling molecules such as transforming growth factor beta and angiotensin II. However, because the pathogenesis of renal fibrosis is extremely complicated and our knowledge regarding this condition is still limited, further studies are needed.

Effects of Direct Cell Contact Between Monocytes and Fibroblasts on the Interleukin-6 Production and Cell Proliferation of Human Gingival and Peri - odontal Ligament Fibroblasts (치은섬유아세포와 치주인대섬유아세포의 interleukin-6 분비 및 세포성장에 미치는 단핵구세포주와 섬유아세포의 세포간 접촉작용)

  • Kim, Soo-Ah;Lee, Ho;Kim, Hyung-Seop;Oh, Kwi-Ok
    • Journal of Periodontal and Implant Science
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    • v.29 no.4
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    • pp.803-823
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    • 1999
  • In order to reveal immunopathogenesis of periodontal tissue destruction, it is important to clarify the molecular mechanism of trafficking and retention of activated leukocytes, including monocytes/macrophages. Gingival fibroblasts may be involved in the regulation of inflammatory cell accumulation in the extravascular periodontal connective tissues via cytokine production and surface expression of adhesion molecules. In this study, it was investigated the molecular basis for the adhesive interactions between monocytes and fibroblasts such as peri-odontal ligament fibroblast(PDLF), human gingival fibroblast(HGF), and human dermal fibroblast(HDF). First, it was examined the evidence whether monocyte-fibroblast cell contact may cause signal transduction in fibroblasts. Being directly in contact with fixed human monocyte cell line THP-1, or U937, upregulation of IL-6 production, $TNF-{\alpha}$ mRNA expression and increased cell proliferation could be seen for fibroblasts. IL-6 production induced by monocyte- fibroblast coculture were further increased when fibroblasts had been pretreated with $IFN-{\gamma}$ or $IL-1{\beta}$ , and monocytes with LPS. Next, it was examined the expression of ICAM-1 which has been known to be involved in accumulation and activation of leukocytes in inflammatory diseases such as periodontitis. ICAM-1 was upregulated up to 10-fold on PDLF, HGF, and HDF by exposure to $IFN-{\gamma}$ or $IL-1{\beta}$. Furthermore, anti-ICAM-1 monoclonal antibody clearly blocked cocultureinduced IL-6 production by fibroblasts, suggesting that $ICAM-1/{\beta}_2$integrin pathway is involved in periodontal fibroblastmonocyte interaction. Overall, these findings provide evidence that periodontal fibroblasts could be involved in the accumulation and retention of monocytes/macrophages in periodontal inflammatory lesion at least in part by ICAM-1 expression. In addition, periodontal fibroblast-monocyte interaction could cause activation signals in fibroblasts intracellularly which result in cytokine production and cell proliferation. Thus, periodontal fibroblasts are speculated to play an important role in immunoregulation and tissue destruction in chronic periodontal diseases by interaction with monocytes/macrophages.

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Genotoxicity Study of Sophoricoside in Bacterial and Mammalian Cell System

  • Yun, Hye-Jung;Kim, Youn-Jung;Kim, Eun-Young;Kim, Youngsoo;Kim, Mi-Kyung;Lee, Seung-Ho;Jung, Sang-Hun;Ryu, Jae-Chun
    • Proceedings of the Korea Society of Environmental Toocicology Conference
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    • 2003.05a
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    • pp.183-184
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    • 2003
  • Sophoricoside was isolated as the inhibitor of IL-5 bioactivity from Sophora japonica (Leguminosae). It has been reported to have an anti-inflammatory effect on rat paw edema model. To develop as an anti-allergic drug, genotoxicity of sophoricoside was investigated in bacterial and mammalian cell system such as Ames bacterial test, chromosomal aberration assay, Comet assay and MOLY assay. In Ames test, sophoricoside of 5000 ∼ 313 $\mu\textrm{g}$/plate concentrations was not shown significant mutagenic effect in Salmonella typhimurium TA98, TA100, TA1535 and TA1537 strains. The cytotoxicity (IC$\_$50/ and IC$\_$20/) of sophoricoside was determined above the concentration of 5000 $\mu\textrm{g}$/ml in Chinese hamster lung (CHL) fibroblast cell and L5178Y mouse lymphoma cell line. At concentrations of 5000, 2500 and 1250 $\mu\textrm{g}$/ml, this compound was not induced chromosomal aberration in CHL fibroblast cell in the absence and presence of S-9 metabolic activation system. Also in comet assay, DNA damage was not observed in L5178Y cell line. Also in MOLY assay, sophoricoside of 5000 ∼ 313 $\mu\textrm{g}$/ml concentrations was not shown significant mutagenic effect in absence of S-9 metabolic activation system. However, the higher concentration of 5000 and 2500 $\mu\textrm{g}$/ml of sophoricoside induced the increased mutation frequency (MF) in the presence of S-9 metabolic activation system. From these results, no genotoxic effects of sophoricoside observed in bacterial systems whereas, genotoxic effects observed in mammalian cell systems in the presence of metabolic activation system. These results suggested that the metabolite(s) of sophoricoside can cause some genotoxic effects in mammalian cells.

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Evaluation of the Genetic Toxicity of Synthetic Chemicals (IV) - in vitro Chromosomal Aberration Assay with 18 Chemicals in Chinese Hamster Lung Cells -

  • Ryu, Jae-Chun;Kim, Kyung-Ran;Kim, Youn-Jung
    • Environmental Mutagens and Carcinogens
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    • v.22 no.3
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    • pp.149-156
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    • 2002
  • The detection of many synthetic chemicals used in industry that may pose a genetic hazard in our environment is of great concern at present. Since these substances are not limited to the original products, and enter the environment, they have become widespread environmental pollutants, thus leading to a variety of chemicals that possibly threaten the public health. In this respect, to regulate and to evaluate the chemical hazard will be important to environment and human health. The clastogenicity of 18 synthetic chemicals was evaluated in Chinese hamster lung fibroblast cells in vitro. 4-Chloro-3,5-dimethyl phenol (CAS No. 88-04-0) induced chromosomal aberrations with significance at the concentration of 15.7 $\mu\textrm{g}$/$m\ell$ both in the presence and absence of metabolic activation system. Phenoxybenzene (CAS No. 101-84-8) which is one of the most cytotoxic chemical among 18 chemicals tested revealed no clastogenicity in the range of 0.11-0.43 $\mu\textrm{g}$/$m\ell$ both in the presence and absence of metabolic activation system. From the results of chromosomal aberration assay with 18 synthetic chemicals in Chinese hamster lung cells in vitro, 4-chloro-3,5-dimethyl phenol (CAS No. 88-04-0) revealed weak positive clastogenic results in this study.

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Fermented Acanthopanax koreanum Root Extract Reduces UVB- and H2O2-Induced Senescence in Human Skin Fibroblast Cells

  • Park, Min-Ja;Bae, Young-Seuk
    • Journal of Microbiology and Biotechnology
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    • v.26 no.7
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    • pp.1224-1233
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    • 2016
  • The present study assessed the effects of an aqueous extract of Acanthopanax koreanum root (AE) and of AE following fermentation by lactic acid bacteria (Lactobacillus plantarum and Bifidobacterium bifidum) (AEF) on human skin fibroblast HS68 cells exposed to ultraviolet B (UVB) irradiation and oxidative stress. AEF effectively antagonized the senescence-associated β-galactosidase staining and upregulation of p53 and p21Cip1/WAF1 induced by UVB or H2O2 treatment in HS68 cells. It also exhibited excellent antioxidant activities in radical scavenging assays and reduced the intracellular level of reactive oxygen species induced by UVB or H2O2 treatment. The antioxidant and antisenescent activities of AEF were greater than those of nonfermented A. koreanum extract. AEF significantly repressed the UVB- or H2O2-induced activities of matrix metalloproteinase (MMP)-1 and -3, overexpression of MMP-1, and nuclear factor κB (NF-κB) activation. This repression of NF-κB activation and MMP-1 overexpression was attenuated by a mitogen-activated protein kinase activator, suggesting that this AEF activity was dependent on this signaling pathway. Taken together, these data indicated that AEF-mediated antioxidant and anti-photoaging activities may produce anti-wrinkle effects on human skin.

Evaluation of the Genetic Toxicity of Synthetic Chemicals (XIV)-in vitro Chromosomal Aberration Assay with 11 Chemicals in Chinese Hamster Lung Cells

  • Kim, Youn-Jung;Ryu, Jae-Chun
    • Molecular & Cellular Toxicology
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    • v.2 no.2
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    • pp.89-96
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    • 2006
  • The detection of many synthetic chemicals used in industry that may pose a genetic hazard in our environment is of great concern at present. Since these substances are not limited to the original products, and enter the environment, they have become widespread environmental pollutants, thus leading to a variety of chemicals that possibly threaten the public health. In this respect, to regulate and to evaluate the chemical hazard will be important to environment and human health. The clastogenicity of 11 synthetic chemicals was evaluated in Chinese hamster lung fibroblast cells in vitro. 1-Chloro-3-bromopropane CAS No. 109-70-6) induced chromosomal aberrations with significance at the concentration of $185.0\;{\mu}g/mL\;and\;1,600\;{\mu}g/mL$ both in the presence and absence of metabolic activation system, respectively. Triphenyl phosphite (CAS No. 101-02-0), which is one of the most cytotoxic chemical among 11 chemicals tested revealed no clastogenicity in the range of $95.0-4.9\;{\mu}g/mL$ both in the presence and absence of metabolic activation system. From the results of chromosomal aberration assay with 11 synthetic chemicals in Chinese hamster lung cells in vitro, 1-chloro-3-bromopropane revealed a positive clastogenic result in this study.

Evaluation of the Genetic Toxicity of Synthetic Chemicals (Ⅶ) -A Synthetic Selective Herbicide, Pendimethalin- (합성화학물질들의 유전독성평가(Ⅶ) -합성 제초제인 Pendimethalin-)

  • Ryu, Jae-Chun;Kim, Kyung-Ran
    • Environmental Analysis Health and Toxicology
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    • v.18 no.2
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    • pp.121-129
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    • 2003
  • The genotoxicity of pendimethalin [N-(l-ethylpropyl)-2, 6-dinitro-3, 4-xylidine, C$\_$13/H$\_$19/N$_3$O$_4$, M.W.=281.3, CAS No. 40487-42-1], one of selective herbicide, was evaluated in bacterial gene mutation system, chromosome aberration in mammalian cell system and in vivo micronucleus assay with rodent. In bacterial gene mutation assay, pendimethalin revealed dose-dependent mutagenic potential in 313 ∼ 5,000 ${\mu}$g/plate of Salmonella typhimurium TA 98 and TA 1537 both in the absence and presence of S-9 metabolic activation system, and TA 100 only in the absence of S-9 mixture. In the TA 1535, slight increase of revertant was also observed in the presence of S-9 metabolic activation system. No mutagenic potential was observed in the TA 1535 without metabolic activation system and TA l00 in the presence of S-9 mixture. In mammalian cell system using Chinese hamster lung (CHL) fibroblast, no clastogenicity of pendimethalin was observed both in the absence and presence of S-9 metabolic activation system in the concentration range of 2.32∼9.28 ${\mu}$g/ml. And also, in vivo bone marrow micronucleus assay, pendimethalin revealed no clastogenic potential in the dose range of 203∼810 mg/kg body weight after oral administration in mice. Consequently, in vitro chromosome aberration with mammalian cells and in vivo bone marrow micronucleus assay revealed no clastogenic potential of pendimethalin. However, pendimethalin revealed mutagenic potential in bacterial gene mutation assay.

Inhibitory Effect of Kamisopunghwalhyeol-tang (Jiaweishufenghuoxie-tang) on Inflammatory Cytokine Production and $NF-{\kappa}B$ and AP-1 Activation in Cultured Humau Fibroblast-like Synoviocytes (가미속풍활형탕이 human fibroblast-like synoviocytes 내 염증 유발 cytokine과 전사인자에 미치는 영향)

  • 양동원;오민석;김동희
    • The Journal of Korean Medicine
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    • v.24 no.3
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    • pp.84-95
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    • 2003
  • Objective : This study was carried out to investigate the effects of Kamisopunghwalhyeol-tang (Jiaweishujenghuoxie-tang; Kami-SPHHT) on the immunity responses of the Synoviocytes isolated from the patients on rheumatoid arthritis. Methods : Cells were stimulated by $Interleukin-1{\beta}$ and Tumor Necrosis $Factor-{\alpha}$ in the presence or absence of Kami-SPHHT, and then induced cytokine mRNA levels were determined by RT-PCR and real-time quantitative RT-PCR. Results : Levels of $IL-1{\beta},{\;}IL-6,{\;}TNF-{\alpha}$, COX-2, and NOS II mRNA expressions significantly decreased in Kami-SPHHT treated cells compared to non-treated control cells. Also, DNA-binding activity of $NF-{\kappa}B$ and AP-l decreased in Kami- SPHHT treated hFLSs. Conclusion : These results suggest that Kami-SPHHT may be involved in anti-inflammatory reactions by inducing cytokine gene expression in synoviocytes, and further in vivo examination on its efficacy can provide potential application for the treatment of rheumatoid arthritis.

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