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Xiuying Liu,
Yibing Huang,
Min Cheng,
Ling Pan,
Youhui Si,
Guirong Li,
Yuqiang Niu,
Lianjing Zhao,
Jin Zhao, Xiang Li,
Yuxin Chen,
Wei Yang
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ABSTRACT: Chronic infection by the hepatitis C virus (HCV) is a cause of the global burden of liver diseases. HCV entry into hepatocytes is a complicated and multistep process that represents a promising target for antiviral intervention. The recently reported amphipathic α-helical virocidal peptide (C5A) from the HCV NS5A protein suggests a new category of antiviral drug candidates. In this study, to identify C5A-like HCV inhibitors, synthetic peptides derived from the C5A corresponding NS5 protein region of selected Flaviviridae viruses were evaluated for their anti-HCV activities. A peptide from GB virus A (GBV-A), but not other flaviviruses, demonstrated an inhibitory effect on HCV infection. Through a series of sequence optimizations and modifications of the peptide helicity and hydrophobicity, we obtained a peptide designated as GBVA10-9 with highly potent anti-HCV activity. GBVA10-9 suppressed both cell culture-derived and pseudotyped HCV infection in vitro, and the 50% cell culture inhibitory concentration ranged from 20 nM to 160 nM, depending on the genotypic origin of the envelope proteins. GBVA10-9 had no detectable effects on either HCV attachment to Huh7.5.1 cells or viral RNA replication. No virucidal activity was found with GBVA10-9, suggesting an action mechanism distinct from C5A. The inhibitory effect of GBVA10-9 appeared to occur at the post-binding step during viral entry. Taken together, GBVA10-9 demonstrated a potent activity for blocking HCV entry that might be used in combination with other antivirals directly targeting virus encoded enzymes. Furthermore, GBVA10-9 also provides a novel tool to dissect the detailed mechanisms of HCV entry.
Journal of Virology 11/2012; · 5.40 Impact Factor
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Linlin Zhang,
Lei Li,
Min Jiao,
Dapeng Wu,
Kaijie Wu, Xiang Li,
Guodong Zhu,
Lin Yang,
Xinyang Wang,
Jer-Tsong Hsieh,
Dalin He
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ABSTRACT: Cancer stem cells (CSCs) are involved in tumorigenesis and progression of prostate cancer (PCa). Conventional anticancer therapeutics failed to eradicate CSCs, which may eventually lead to the disease relapse and metastasis. Therefore, targeting prostate CSCs may be an ideal strategy to cure PCa. Genistein is a major isoflavone constituent of soybeans and soy products, which has been shown to exhibit potent anticancer effect on many cancers. We have previously reported that genistein can inhibit PCa cell invasion by reversing epithelial to mesenchymal transition, suggesting that genistein may be effective against metastatic PCa. In addition, we have recently demonstrated that PCa tumorsphere cells (TCs) possess CSC properties. Here, we found that tumorsphere formation and colony formation of Pca cells were noticeably suppressed in the presence of genistein. Pretreatment of PCa TCs with genistein also suppressed tumorigenicity in vivo. Additionally, genistein treatment inhibited tumor growth of PCa TCs. Further studies showed that genistein treatment not only led to the down-regulation of PCa CSC markers CD44 in vitro and in vivo, but also inhibited Hedgehog-Gli1 pathway, which may contribute to the anti-CSC effect of genistein in PCa TCs. Therefore, our findings demonstrated that genistein may be a dietary phytochemical with potential to target prostate CSCs.
Cancer letters 04/2012; 323(1):48-57. · 4.86 Impact Factor
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Fei Yan, Xiang Li,
Qiaofeng Jin,
Juanjuan Chen,
Robin Shandas,
Junru Wu,
Lu Li,
Tao Ling,
Wei Yang,
Yun Chen,
Xin Liu,
Hairong Zheng
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ABSTRACT: This study is designed to investigate the feasibility for molecular imaging of endothelial CD81 expression in vitro and in vivo using the CD81-targeted ultrasound contrast agents (UCA). In the in vitro study, murine bEnd.3 cells were stimulated with phenazine methosulfate (PMS), an oxidative stress inducer. Changes in CD81 expression after stimulation were confirmed by Western blotting, tracked by using the targeted UCA and further imaged under ultrasound imaging system with 5 MHz transmit frequency. In the in vivo study, expression of endothelial CD81 proteins in murine carotid artery vessels was studied using high-frequency ultrasound system with 40 MHz transmit frequency. Our results showed that endothelial CD81 expression was gradually up-regulated with the increase of PMS concentration. Correspondingly, the accumulation of targeted UCA was gradually improved and could be inhibited significantly upon addition of free anti-CD81 antibodies. The mean video intensity (grey-level) of stimulated cells and vessels from backscatter of the CD81-targeted UCA was 17.2 (interquartile range [IQR] 15.4-19.8) and 27.2 (IQR 22.4-29.8), significantly greater than that of non-stimulated cells with 9.0 (IQR 8.6-10.8) (p < 0.01) and non-stimulated vessels with 11.3 (IQR 10.4-13.2) (p < 0.01), respectively. In conclusion, CD81-targeted UCA allows noninvasive assessment of the expression levels of CD81 on the vascular endothelium and may provide potential insights into early atherosclerotic plaque detection and treatment monitoring.
Ultrasound in medicine & biology 04/2012; 38(4):670-80. · 2.02 Impact Factor
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03/2012; , ISBN: 978-953-51-0403-2
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ABSTRACT: Interleukin 28B (IL28B) genetic variation has been recently reported as a potent predictor of hepatitis C virus (HCV) response to interferon (IFN) therapy. The aim of this study was to produce recombinant human IL28B (rhIL28B) in yeast and explore the action mechanisms of rhIL28B as a novel anti-HCV agent.
A simple and efficient protocol for producing rhIL28B in the methylotrophic yeast Pichia pastoris was developed. The anti-HCV activity, induction of IFN-stimulated genes (ISGs), receptor usage and cellular responsiveness of rhIL28B were characterized.
The yield of secreted rhIL28B was optimized to 200 mg/L, and soluble rhIL28B that was approximately 95% pure was achieved using a one-step ion-exchange purification procedure. rhIL28B inhibited HCV propagation in Huh7.5.1 cells with an IC(50) of 0.15 × 10(-3) mg/L. Treatment of hepatoma cells with rhIL28B resulted in the phosphorylation of STAT1 within 1 h and expression of ISGs. The HCV inhibitory effects of rhIL28B were antagonized by the antibody neutralization of receptors IL10R2 and IL28R1. The combination of rhIL28B and ribavirin synergistically inhibited HCV production in cell culture. Importantly, compared with the broad-spectrum activity of IFN-α, we demonstrated restricted cell-type responsiveness of rhIL28B in liver, lung and prostate cells.
This study established an easy and highly efficient approach for the production of rhIL28B with potent in vitro antiviral activity and restricted cell tropism, and thus provides a novel antiviral candidate for improving the treatment of HCV-infected patients.
Journal of Antimicrobial Chemotherapy 02/2012; 67(5):1080-7. · 5.07 Impact Factor
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Linlin Zhang,
Min Jiao,
Lei Li,
Dapeng Wu,
Kaijie Wu, Xiang Li,
Guodong Zhu,
Qiang Dang,
Xinyang Wang,
Jer-Tsong Hsieh,
Dalin He
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ABSTRACT: Prostate cancer (PCa) becomes lethal when cancer cells develop into castration-resistant PCa, which remains incurable because of the poor understanding of their cell origin and characteristics. We aim to investigate the potential role of cancer stem cells (CSCs) in PCa progression.
Human PCa cell lines (LNCaP, 22RV1, DU145 and PC-3) were plated in serum-free suspension culture system allowed for tumorsphere forming. To evaluate the CSC characteristics of tumorspheres, the self-renewal, chemoresistance, tumorigenicity of the PCa tumorsphere cells, and the expression levels of stemness-related proteins in the PCa tumorsphere cells were assessed, comparing with the parental adherent cells.
Tumorsphere cells from PCa cell lines displayed enhanced self-renewal, chemoresistance and tumor-initiating capacity when compared with the adherent cells. Additionally, these cells overexpressed CSC marker CD44. Also, the tumorsphere cells expressed high levels of "stemness" genes Gli1, ABCG2 and Bmi-1.
Collectively, these data demonstrated that tumorspheres derived from PCa cells possess chemoresistant and CSC properties. Our study suggests that the identification of PCa CSCs could provide new insight into the lethal phenotype of PCa and therapeutic implications.
Journal of Cancer Research and Clinical Oncology 01/2012; 138(4):675-86. · 2.56 Impact Factor
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ABSTRACT: Insects attracted to cadavers may provide important indications of the postmortem interval (PMI). However, use of the flesh flies (Diptera: Sarcophagidae) for PMI estimation is limited as the species are often not morphologically distinct, especially as immatures. In this study, 23 forensically important flesh flies were collected from 13 locations in 10 Chinese provinces. Then, a 278-bp segment of the cytochrome oxidase subunits one (COI) gene and a 289-bp segment of the 16S rDNA gene of all specimens were successfully sequenced. Phylogenetic analysis of the sequenced segments showed that all sarcophagid specimens were properly assigned into four species (Boerttcherisca peregrina [Robineau-Desvoidy, 1830], Helicophagella melanura [Meigen, 1826], Parasarcophaga albiceps [Meigen, 1826], and Parasarcophaga dux [Thompson, 1869]) with relatively strong supporting values, thus indicating that the COI and 16S rDNA regions are suitable for identification of sarcophagid species. The difference between intraspecific threshold and interspecific divergence confirmed the potential of the two regions for sarcophagid species identification.
Journal of Forensic Sciences 08/2011; 56(6):1534-40. · 1.23 Impact Factor
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ABSTRACT: Species identification of sarcosaphagous insects is one of the important steps in forensic research based on the knowledge of entomology. Recent studies reveal that the application of molecular biology, especially the mtDNA sequences analysis, works well in the species identification of sarcosaphagous insects. The molecular biology characteristics, structures, polymorphism of mtDNA of sarcosaphagous insects, and the recent studies in species identification of sarcosaphagous insects are reviewed in this article.
Fa yi xue za zhi 04/2011; 27(2):133-8.
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ABSTRACT: To investigate SiO2-induced EMT in human bronchial epithelial cells HBE in vitro.
HBE cells were cultured and then stimulated with indicated doses of SiO2 (0, 50, 100, 200, 300 µg/ml). The morphological changes were observed by microscope. In addition, Western blot was per-formed to detect the expression of E-cad, α-SMA and Vim. The changes of migration ability were examined by wound-healing assay in vitro.
(1) After exposure to SiO2, HBE cells lost contact with their neighbor and displayed a spindle-shape, fibroblast-like morphology. (2) Compared with the control, the E-cad (300 µg/ml group) expression downregulated 2.98 fold (P < 0.05), and the Vim (300 µg/ml group) and α-SMA (200 µg/ml group) expression upregulated 4.46 fold and 3.55 fold (P < 0.05). There were significant differences between 100, 200, 300 µg/ml groups and the control group (P < 0.05). (3) In the test group, the percentage of wound-healing areas/wound areas were larger than those in control group (P < 0.05).
SiO2 could induce EMT in human bronchial epithelial cells.
Zhonghua lao dong wei sheng zhi ye bing za zhi = Zhonghua laodong weisheng zhiyebing zazhi = Chinese journal of industrial hygiene and occupational diseases 01/2011; 29(1):7-10.
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ABSTRACT: To explore mitochondrial DNA (mtDNA) extraction effects of different parts from sarcosaphagous insects using improved cetyltriethylammnonium bromide (CTAB) method.
Thirteen Lucilia sericata (Meigen) and 13 Nicrophorus fossor (Erichson) were collected from the corpses of rabbits placed on the outdoor lawn in Huhehot district. Four parts (head, chest muscle, legs and wings) of insect were collected, and the mtDNA of all samples were extracted using CTAB method. The purity and concentration were tested using protein and nucleic acid spectrophotometry. The integrity of the extracted mtDNA and PCR products were checked by agarose gel electrophoresis. The PCR products were sequenced and the obtained sequences were imputed into GenBank for comparison.
mtDNA were successfully extracted from 10 head samples, 6 legs samples, 4 wing samples and 13 chest muscle samples of the Lucilia sericata (Meigen). Also, mtDNA were successfully extracted from 5 head samples, 8 legs samples, 3 wing samples and 13 chest muscle samples of the Nicrophorus fossor (Erichson).
mtDNA can be obtained from chest muscle and other parts of sarcosaphagous insects using the improved CTAB method.
Fa yi xue za zhi 10/2010; 26(5):336-9.
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ABSTRACT: To study the succession of sarcosaphagous insects and their regular activity on carcass in Shijiazhuang area.
Nine rabbits were sacrificed and placed at the same site during June to September in 2007-2009. The common species of sarcosaphagous insects were observed.
Nine main species could be identified belonging to 3 families and 4 genera from Diptera, including Musca domestica (Linnaeus), Muscina stabulans (Fall én), Hydrotaea (Ophyra) capensis (Wiedemann), Hydrotaea (Ophyra) spinigera (Stein), Lucilia sericata (Meigen), Chrysomya megacephala (Fabricius), Boerttcherisca Peregrina (Robineau-Desvoidy), Parasarcophaga crassipalpi (Macquart) and Helicophagella melanura (Meigen). Eleven main species belonging to 4 families from Coleoptera include Nicrophorus concolor (Kraatz), Silpha carinata(Herbst), Nicrophorus fossor (Eneshas), Ptomascopus morio (Kraatz), Eusilpha bicolor (Fairmaire), Scarabaeus rugosus (Hausmann), Harpalus rufipes (DeGeer), Dolichus halensis (Schaller), Goncephalum pusillum (Fabricius), Cafius seminitens (Horn) and Aleochara pacifica (Casey). Two main species from 2 families were Tetramorium caespitum (Linnaeus) and Vespa velutina(Lepeletier).
It is evident that the succession of sarcosaphagous flies in Shijiazhuang with its unique geographical features. It may be used for estimating postmortem interval in Shijiazhuang area.
Fa yi xue za zhi 08/2010; 26(4):253-6.
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Bo Li, Xiang Li,
Yingxin Li,
Hui Guo,
Shu-Yan Sun,
Qiong-Qiong He,
Ying Wang,
Junming Luo,
Ji-Fang Wen,
Hui Zheng,
De-Yun Feng
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ABSTRACT: Hepatitis C virus (HCV) infection has become a severe health problem worldwide. The viral proteins are believed to be among the most important factors that contribute to HCV mediated pathogenesis. Accumulated evidence demonstrating that HCV non-structural protein 3 (NS3) possesses oncogenic potential, and is involved in the regulation of cell proliferation has been documented. In this study, we emphasized the effect of HCV NS3 protein on cell proliferation in the immortally normal hepatocyte QSG7701 cells. The cell line transfected with plasmid expressing NS3 protein showed enhanced cell growth, extracellular signal-related kinase (ERK) activation, DNA binding activities of transcription factors of activator protein 1 (AP-1) and NF-kappaB, and cyclin D1 overexpression, but without activation of Jun amino-terminal kinase or p38. Pre-treatment of NS3 protein expressing cells with ERK inhibitor, PD98059, blocked the activation of AP-1 and NF-kappaB, and inhibited cyclin D1 expression and cell proliferation. The results suggest that NS3-mediated cell growth occurs through activation of ERK/AP-1 and NF-kappaB/cyclin D1 cascades.
International Journal of Molecular Medicine 08/2010; 26(2):273-9. · 1.98 Impact Factor
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ABSTRACT: The cytokines secreted by lung macrophages have been shown to play a critical role in the pathogenesis of silicosis, tumor necrosis factor-alpha (TNF-alpha), and transforming growth factor-beta1 (TGF-beta1) are prominent cytokines in silicosis, but the underlying mechanism remains to be determined. The aim of the present study was to investigate the roles of Src-mitogen-activated protein kinase (MAPKs)/activator protein-1 (AP-1) signaling pathways in silica-induced TNF-alpha and TGF-beta1 expression in macrophage cells (RAW264.7). It was found that silica activated Src, p38 kinase, and extracellular signal-regulated kinase (ERK) in RAW264.7 cells. The induction of TNF-alpha and TGF-beta1 by silica was suppressed by Src inhibitor (PP1), ERK inhibitor (PD98059), but not by p38 kinase inhibitor (SB203580). Dominant negative mutant c-Jun (TAM67) inhibited silica-induced AP-1 DNA binding activity and downregulated the TNF-alpha and TGF-beta1 expression. In addition, PD98059 but not SB203580 inhibited the AP-1 DNA binding activity induced by silica. Based on these findings, it was conclude that Src-ERK/AP-1 signaling pathways are involved in the TNF-alpha and TGF-beta1 expression induced by silica in macrophages.
Toxicology mechanisms and methods 01/2009; 19(1):51-8. · 1.03 Impact Factor
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Zhongyuan Jin,
Baoan Liu,
Deyun Feng,
Chen Chen, Xiang Li,
Yongbin Hu,
Jinwu Peng,
Yu Liu,
Jing Du,
Chunyan Fu,
Jifang Wen
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ABSTRACT: The critical molecular mechanism in the development of the pulmonary fibrosis remains unknown, leaving diagnosed patients with a poor prognosis. To isolate the genes specifically up-regulated in pulmonary fibrosis, we established a rat silicosis model 360 d after treatment with crystalline silica suspension. Radiographs of chests showed that some scattered high-density shadows appeared in the lung field. Typical microscopic fibrosing silicotic nodules formed in the lung, alveolar epithelial cells and bronchial epithelial cells, particularly around the partial fibrosing silicotic nodules; some of them showed atypical hyperplasia that suggested a correlation between silicosis and lung cancer. Suppression subtractive hybridization analysis was performed to compare gene expression in lung tissue with silicosis and normal lung tissue. Reverse transcription-polymerase chain reaction showed that the expressions of seven novel cDNA sequences identified by suppression subtractive hybridization in lung tissue with silicosis differed from normal lung tissue. Bioinformatics analysis showed that 47 positive clones represented 35 genes containing two putative proteins and four predicted similar proteins. The analysis also showed that some screened genes in silicosis, such as prolyl 4-hydroxylases, actin-related protein-2/3 complex and acidic mammalian chitinase, have not been previously reported. These genes may provide new clues for investigating the molecular mechanisms in the development of pulmonary fibrosis.
Acta Biochimica et Biophysica Sinica 09/2008; 40(8):740-6. · 1.38 Impact Factor
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ABSTRACT: To investigate the role of extracellular signal-regulated kinase (ERK)/activator protein-1 (AP-1) signaling pathway in SiO(2)-induced plasminogen activators inhibitor-1 (PAI-1) protein expression in human lung epithelial cells A549.
A549 cells were cultured and then stimulated with 200 microg/ml SiO(2) for 0 approximately 24 h. To prevent AP-1 activity, Curcumin was added into culture medium before incubating with SiO(2) and transient TAM-67 transfection was performed. In addition, PD98059 was pretreated with cells to prevent ERK activity. The PAI-1 protein expression and ERK activity were evaluated by Western blot. The AP-1 DNA binding activity was tested by EMSA.
(1) At 4, 8 and 16 h after exposure to SiO(2), the fold change of AP-1 DNA binding activity (relative to the control group) were 1.3, 1.3, and 2.1, respectively (P < 0.05). 10, 25, 50 micromol/L Curcumin inhibited SiO(2)-induced PAI-1 protein expression (inhibition ratio: 20%, 63%, 65%; P < 0.05). TAM-67 downregulated SiO(2)-induced PAI-1 protein expression (inhibition ratio: 59%, P < 0.05). (2) SiO(2) activated ERK and PD98059 downregulated SiO(2)-induced PAI-1 protein expression (inhibition ratio: 51%, P < 0.05). (3) PD98059 downregulated SiO(2)-induced AP-1 DNA binding activity (inhibition ratio: 73%, P < 0.05).
ERK/AP-1 signaling pathway is responsible for SiO(2)-induced PAI-1 protein expression.
Zhonghua lao dong wei sheng zhi ye bing za zhi = Zhonghua laodong weisheng zhiyebing zazhi = Chinese journal of industrial hygiene and occupational diseases 07/2008; 26(7):387-90.
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ABSTRACT: To study the role of activator protein-1 (AP-1) in the up-regulation expression of tumor necrosis factor-alpha (TNF-alpha) and transforming growth factor-beta1(TGF-beta(1)) in silica-stimulated macrophage cells (RAW264.7).
RAW264.7 cells were treated with AP-1 inhibitor Curcumin. The expression of c-jun and c-fos in nuclear protein was detected by western blotting. The level of TNF-alpha and TGF-beta(1) protein in the cell supernatant was measured using enzyme-linked immunoadsorbent assay (ELISA). Meanwhile the expression of TNF-alpha and TGF-beta(1) mRNA was also monitored by reverse transcriptase-polymerase chain reaction (RT-PCR).
The nucleoprotein expression of c-jun and c-fos in 10 and 20 micromol/L Curcumin prevention group (1.150 +/- 0.020, 1.010 +/- 0.108, 80.430 +/- 0.023, 0.256 +/- 0.015) were lower than those in silica-stimulated group (1.550 +/- 0.029, 0.860 +/- 0.036) (P < 0.01). In 20 micromol/L Curcumin prevention group and silica stimulated group, the expression of TNF-alpha protein were 23.58 +/- 45.78 and 32.12 +/- 5.34, and the expression of TGF-beta(1) protein were 1582.18 +/- 437.52 and 55.60 +/- 5.51 (P < 0.05 =; the expression of TNF-alpha, TGF-beta(1) mRNA were 0.74 +/- 0.01, 0.22 +/- 0.04 and 2.27 +/- 0.33, 2.96 +/- 0.15 (P < 0.05 =.
The expression of TNF-alpha, TGF-beta(1) mRNA and proteins is associated with activation of AP-1 in silica-stimulated macrophage cells.
Zhonghua lao dong wei sheng zhi ye bing za zhi = Zhonghua laodong weisheng zhiyebing zazhi = Chinese journal of industrial hygiene and occupational diseases 02/2008; 26(1):12-5.
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ABSTRACT: To investigate the role of AP-1 in the secretion of Type I collagen in TGF-beta1-stimulated human lung fibroblasts.
Human lung fibroblasts cell line (HLF-02) was cultured, and then stimulated with 10 microg/L TGF-beta1 at different time points. Curcumin was added into the culture medium to inhibit the AP-1 activity before incubating with TGF-beta1. AP-1 DNA binding activity was assayed by electrophoretic mobility shift assay (EMSA), and the expression of Type I collagen was detected by Western blot and RT-PCR.
TGF-beta1 could induce the transcription and secretion of Type I collagen in HLF-02 cells(P<0.05). TGF-beta1 could upregulate the AP-1 DNA binding activity ( P<0.05). Curcumin ( 5, 10, 15, and 20 micromol/L) could inhibit the AP-1 DNA binding activity in TGF-beta1-stimulated cells (the inhibition ratio was 17.1%, 17.6%, 24.2%, and 31.3%; P<0.05). Curcumin (5, 10, 15, and 20 micromol/L) could also inhibit the secretion of Type I collagen significantly (the inhibition ratio was 62.1%, 58.8%, 62.1%, and 59.6%; P<0.05).
AP-1 is responsible for the secrection of TGF-beta1-induced Type I collagen in human lung fibroblasts.
Zhong nan da xue xue bao. Yi xue ban = Journal of Central South University. Medical sciences 10/2007; 32(5):776-81.
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ABSTRACT: To investigate the effects of SiO(2) on the expression of alpha-smooth muscle actin (alpha-SMA) in human lung fibroblasts in vitro and vivo.
The experimental group comprised 32 rats while 32 rats were included in the control. In vivo, the expression of alpha-SMA in lung tissues of rats exposed to SiO(2), the supernate of RAW264.7 cells, SiO(2) and the growth factor beta(1) (TGF-beta(1)) were investigated, respectively.
(1) alpha-SMA positive myofibroblasts appeared in the lung tissues of the 28th day groups exposed to SiO(2). (2) The expression of alpha-SMA in HLF-02 cells was unregulated by TGF-beta(1) and supernate of RAW264.7 cells exposed to SiO(2). (3) The expression of alpha-SMA in HLF-02 cells was not induced by SiO(2).
Myofibroblasts related to silicosis, and the appearance of myofibroblasts (in vitro) are independent on direct stimulation by SiO(2), but related to the mediator (TGF-beta(1)) secreted by SiO(2) stimulated macrophages.
Zhonghua lao dong wei sheng zhi ye bing za zhi = Zhonghua laodong weisheng zhiyebing zazhi = Chinese journal of industrial hygiene and occupational diseases 10/2006; 24(9):523-5.
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ABSTRACT: To explore the changes of apoptosis of cells in the lung tissue of rats with silica instillation and to its significance in silicosis, and to clarify the role of caspase-3 in the apoptosis progress.
Forty-eight rats were randomly divided into saline control groups and silica instillation groups, and the silicosis model was established in rats. Flow cytometry was used for detecting the rate of apoptosis at various stages. Immunohistochemistry for the expression of cleaved caspase-3.
The model of rat silicosis was established successfully. The apoptosis rate in the experimental group was significantly higher than that in the control group, and was increased with time. Caspase-3 was mainly expressed in alveolar epithelium cells, pulmonary macrophages and infiltrated inflammation cells. The expression of caspase-3 in the experimental group was stronger than that in the control group, but its expression intensity was not related to the cell apoptosis (r = 0.215, P > 0.05).
The apoptosis of the lung cells plays an important role during rat silicosis genesis. Caspase-3 plays an important role in regulating cell apoptosis during rat silicosis genesis.
Zhong nan da xue xue bao. Yi xue ban = Journal of Central South University. Medical sciences 08/2005; 30(4):441-3.
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ABSTRACT: To study the correlation between the expression of Egr-1 and NF-kappaB and the up-regulation of TNF-alpha and TGF-beta1 in macrophages after stimulation by silica in-vitro.
Macrophages were treated with antibodies against Egr-1 and NF-kappaB and antisense oligonucleotides. The level of TNF-alpha protein in the cell supernatant was then measured using enzyme-linked immunoadsorbent assay (ELISA). The expression of TGF-beta1 protein was detected by immunocytochemistry. The expression of TNF-alpha and TGF-beta1 mRNAs was also monitored by reverse transcriptase-polymerase chain reaction (RT-PCR).
Compared with silica-stimulated macrophages untreated with antibodies, the cells treated with 10 micro g/ml of Egr-1 or NF-kappaB antibodies were associated with reduced expression of TNF-alpha and TGF-beta1 proteins and mRNAs (P < 0.05). Compared with silica-stimulated untransfected group, the antisense group was associated with obvious reduction in the expression of TNF-alpha and TGF-beta1 proteins and mRNAs (P < 0.05).
The expression of TNF-alpha and TGF-beta1 mRNAs and proteins are associated with activation of Egr-1 and NF-kappaB in macrophages, after stimulation by silica. It is possible that the corresponding antibodies and antisense oligonucleotides may become a potential therapeutic tool in the management of silicosis in the future.
Zhonghua bing li xue za zhi Chinese journal of pathology 08/2004; 33(4):363-7.
