Successful treatment of experimental autoimmune myocarditis by adenovirus-mediated gene transfer of antisense C Ⅱ TA

Experimental autoimmune myocarditis （EAM） has been used as a model for human myocarditis in relation to the autoimmune mechanism and proved as a T cell mediated autoimmune disease. Interaction of T cell receptors （TCR） with its ligand peptide-MHC complex on APCs is critical for antigen-specific T cell activation under physiological and pathological conditions.     

VIR576通过与TCR跨膜区结合抑制抗原特异性T细胞活化

目的 探讨抗HIV多肽VIR576抑制抗原特异性T细胞活化的作用机制.方法 OVA体外刺激分离的DO11.10小鼠抗原特异性T细胞,CCK-8法检测VIR576对其活化的影响.采用溶血试验,溶血抑制实验、荧光结合法等方法检测VIR576与TCR跨膜区序列(TCR-TMD)之间的相互作用.结果 体外实验显示,VIR576能逆转HIV gp41融合多肽(FP)介导的抗原特异性T细胞活化,并且其自身也能抑制抗原特异性的T细胞活化(P<0.05).溶血试验、溶血抑制实验、荧光结合法等方法证实,VIR576能与TCR-TMD特异性结合.结论 VIR576对T细胞活化的作用是TCR依赖性的,通过与TCR-TMD结合抑制抗原特异性T细胞活化.VIR576兼具抑制HIV进入和抗原特异性T细胞活化的特性,可望作为预防HIV性传播的杀微生物剂进行研究.

Abstract：

Objective To study the mechanism underlying the inhibitory effect of the anti-HIV peptide VIR576 on antigen-specific T cell activation. Methods CCK-8 assay was used to investigate the effect of VIR576 on the proliferation of splenocytes of OVA-specific DO11.10 Tg mice in response to chicken OVA. Hemolysis test, hemolysis inhibition assay and fluorescence binding assay were used to investigate the interaction of VIR576 with the transmembrane domain (TMD) of the T cell receptor (TCR). Results VIR576 inhibited HIV glycoprotein gp41 fusion peptide-mediated antigen specific T cell activation, and VIR576 itself also inhibited splenocyte proliferation in responses to OVA (P<0.05). Hemolysis test, hemolysis inhibition assay and fluorescence binding assay demonstrated that VIR576 suppressed TCR-TMD-mediated hemolysis and competitively inhibited Rho-VIR576 binding to TCR-TMD peptide. Conclusion VIR576 is effective in suppressing the antigen-specific T cell activation via TCR and can interact with TCR-TMD. VIR576 may serve as a potent microbicide candidate to block sexual transmission of HIV due to of its inhibitory effect on both HIV entry and antigen-specific T cell activation.     

A therapeutic anti-CD4 monoclonal antibody inhibits T cell receptor signal transduction in mouse autoimmune cardiomyopathy

Background T cell immune abnormalities in patients with dilated cardiomyopathy (DCM) has been intensively studied over the past 10 years. Our previous study has suggested that immunization of mice with the peptides derived from human adenine nucleotide translocator (ANT) result in the production of autoantibodies against the ANT and histopathological changes similar to those in human DCM. The ANT peptides can induce autoimmune cardiomyopathy like DCM in Balb/c mice. In this study we aimed to focus on the molecular mechanism of T cells in the autoimmune cardiomyopathy mouse model by detecting the expression of the two T cell signaling molecules.Methods The ANT peptides were used to cause autoimmune cardiomyopathy in Balb/c mice. Anti-L3T4 or rat anti-mouse IgG was administered to the mice (n=6 in each group) simultaneously immunized with ANT. ELISA analysis was used to detect autoantibodies against the ANT peptides and the percentages of interferon-γ and interleukin-4 producing cells among splenic CD4(+) lymphocytes was determined by using flow cytometry analysis. The expression of CD45 in spleen T cells was determined by immunohistochemistry and the mRNAs of T cell signaling molecules were detected by real-time PCR.Results Treatment of ANT immunized Balb/c mice with anti-CD4 mAb caused a reduction in the gene expression of P56lck and Zap-70 and a lower level of CD45 expression by spleen T cells. Also, a reverse of the Th1/Th2 ratio that results in the reduced production of antibodies against ANT was found in the anti-CD4 monoclonal antibodies (mAb) group. Whereas irrelevant antibody (rat anti-mouse IgG) did not suppress T cell signaling molecules nor inhibit CD45 expression, and control-antibody mice did not show any significant differences compared with the DCM group.Conclusion The results show that anti-CD4 mAb is a powerful inhibitor of the early initiating events of T cell receptor (TCR) signal transduction in mouse autoimmune dilated cardiomyopathy.     

Expression of IL-βα and TNF-α in MCMV Myocarditis and Its Role

In order to study the expression of IL-β and TNF-α in the myocardium of MCMV myocarditis and their role in the myocardial damages, 60 BALB/C mice of 4 weeks were randomly divided into two groups: 36 were injected intraperitoneally with MCMV and 24 served as control group. Immunohistochemistry was used to detect IL-β and TNF-α expression in the myocardium, and myocardial lesions were observed histopathologically. Histopathological study on the myocardium from infected mice revealed focal or diffuse lesions characterized by inflammatory cells and degeneration or necrosis of myocytes. The myocardial lesion score showed the degree of inflammatory cell infiltration was slight in MCMV myocarditis. The positive staining signals for IL-β and TNF-α proteins which mainly located in the infiltrating inflammatory cells and degenerative or necrotic myocytes were markedly detectable whereas there were no positive findings in the myocardium of control mice. IL-β and TNF-α was expressed in the myocardium of viral myocarditis murine model induced by MCMV. IL-β and TNF-α may play an important role in the pathogenesis of viral myocarditis.     

Effect of emodin on proliferation and differentiation of 3T3-L1 preadipocyte and FAS activity

Objective To study the effects of emodin on proliferation and differentiation of 3T3-L1 preadipocyte and the possible mechanism.Methods Cell proliferation was determined by MTT spectrophotometry, cell differentiation was determined by Oil Red O staining, and fatty acid synthase (FAS) activity was determined by spectrophotometry.Results Emodin promoted proliferation of 3T3-L1 preadipocyte at low concentration and inhibited the proliferation at high concentration in a dose-related manner.In contrast, it inhibited cell differentiation into adipocyte at low concentration in a dose-related manner.In vitro emodin inhibited the activity of FAS in a dose-related manner.Conclusions The effects of emodin on 3T3-L1 cell’s proliferation and differentiation are dose dependent.Emodin inhibits the activity of FAS.Our results suggest that emodin should have a potential to serve as a fat-reducing drug.     

Selective depletion of non-specific T cells as an early event in T cell response to bacterial and viral infections

Early T cell depletion occurs prior to the development of an effective immune response to infections.Both antigen-specific and non-specific T cells are induced to express early activation markers soon after microbial infections.This is followed by massive depletion of non-specific T cells and extensive proliferation of antigen-specific T cells.Proliferating antigen-specific cells exhibit a broad spectrum of late activation markers while non-specific cells exhibit no sign of further activation before succumbing to apoptosis.These results have crucial implications for the understanding of early events in the development of a robust T cell response.     

Potent antitumor efficacy of an E1B 55kDa-deficient adenovirus carrying murine endostatin in hepatocellular carcinoma

Data from clinical trails have shown that the antitumoral effect of ONYX-015, an E1B 55kDa-deficient adenovirus, as monotherapy is insufficient. To enhance its efficiency, CNHK200-mE, another E1B 55kDa-deficient adenovirus armed with a mouse endostatin gene was constructed and its antitumoral activities against hepatocellular carcinoma （HCC） in vitro and in vivo were investigated. The selective replication and cytotoxicity of CNHK200-mE in Hep3B and HepG Ⅱ cells independent of p53 status were confirmed via TCID50 and 3-（4,5dimetylthiazol）-2,5-diphenyltetrazolium bromide （MTT） assays. Potent tumor growth suppression on SMMC-7721 xenografts in nude mice was observed and a synergistic effect of the carrier virus and the therapeutic gene was suggested. Moreover, in comparison with. the nonreplicative adenovirus carrying the same therapeutic gene, amplified transgene expression of mouse endostatin in vitro and in vivo were confirmed by Western blotting and ELISA assay. The effective angiogenesis inhibition and replication of CNHK200-mE in nude mice xenografts were demonstrated by immunohistochemistry. In conclusion, the recombinant adenovirus CNHK200-mE is a replication-competent oncolytic virus mediating high expression of therapeutic gene. Because CNHK200-mE is capable of replicating in and lysing HCC cells selectively with effective tumor growth suppression and antiangiogenic activity on HCC xenografts in nude mice, it holds good potential for the treatment of HCC.     

Combined Use of RGD-peptide Modified PLGA and TGF-β1 Gene Transfected MSCs to Improve Cell Biobehaviors in vitro

In order to improve the surface properties of PLGA polymer for a better material/cell interface to modulate the cells behaviors, we prepared a novel three-block copolymer, PLGA-[ASP-PEG], and immobilized an RGD-containing peptide, Gly-Arg-Gly-Asp-Ser-Pro-Cys （GRGDSPC） on the surface of it. Transforming growth factor-β1 （TGF-β1） was transfected into bone marrow stromal cells （MSCs） employed as seeded cells. Cell adhesion, spreading, proliferation and differentiation on this material were investigated. The results showed that the cell adhesive ratio on RGD-modified materials was higher than on un-modified materials （P〈0.05）. The extent of cell spreading was also wider on RGD-modified materials than on un-modified materials. Cell proliferation indices of transfected MSCs were increased as compared with the un-transfected MSCs （P〈0.05）. The ALP activities in the MSCs cultured with RGD-modified materials were higher than on un-modified materials after 14 days （P〈0.05）, and those in transfected MSCs were higher than in un-transfected MSCs （P〈0.05）. It was suggested that the combined use of RGD-modification and TGF-β gene transfection could improve the interaction of biomaterial and cells.     

A Novel Chitosan CpG Nanoparticle Regulates Cellular and Humoral Immunity of Mice

Objective To develop a safe and novel immunoadjuvant to enhance the immunity and resistance of animals against E. coli infection. Methods An 88-base immunostimulatory oligodeoxynuleotide containing eleven CpG motifs （CpG ODN） was synthesized and amplified by PCR. The chitosan nanoparticle （CNP） was prepared by ion linking method to entrap the CpG ODN that significantly promotes the proliferation of lymphocytes of pig in vitro. Then the CpG- CNP was inoculated into 21-day old Kunming mice, which were orally challenged with virulent K88/K99 E. Coil 35 days after inoculation. Blood was collected from the tail vein of mice on days 0, 7, 14, 21, 28, 35, 42, and 49 after inoculation to detect the changes and content of immunoglobulins, cytokines and immune cells by ELISA, such as IgG, IgA, IgM, IL-2, IL-4, and IL-6. Results The CpG provoked remarkable proliferation of lymphocytes of pig in vitro in comparison with that of control group （P〈0.05）. The inoculation with CpG-CNP significantly raised the content of IgG, IgM, and IgA in the sera of immunized mice （P〈0.05）. The levels of IL-2, 1L-4, and IL-6 in the mice significantly increased in comparison with those in controls （P〈0.05）, so was the number of white blood cells and lymphocytes in immunized mice. The humoral and cellular immunities were significantly enhanced in immunized mice, which resisted the infection of E coli and survived, while the control mice manifested evident symptoms and lesions of infection. Conclusions CpG-CNP can significantly promote cellular and humoral immunity and resistance of mice against E. coli infection, and can be utilized as an effective adjuvant to improve the immunoprotection and resistance of porcine against infectious disease.     

Effect of verapamil on acute coxsackievirus B3 murine myocarditis.

The effect of verapamil (Ver) on CVB3 murine myocarditis was investigated. It was found that Ver could aggravate the myocardial inflammation, increase the viral replication in myocardium, and raise mortality in mice with viral myocarditis when the drug was injected within the first 6 days after the CVB3 inoculation.

     

Synergistic antitumor effects of in vivo production of human endostatin and tissue inhibitor of metalloproteinase-1 in mice after subcutaneous implantation of primary fibroblasts transfected by adenovirus-mediated gene delivery

Background Tissue inhibitor of metalloproteinase （TIMP）-1 is a multifunctional protein. The aim of the study was to examine the feasibility of using a combination of adenovirus-mediated gene delivery of TIMP-1 plus endostatin and cell transplantation techniques to treat tumor growth and metastasis in mouse melanoma.Methods A enzyme-linked immunosorbent assay （ELISA） was used to detect the level of TIMP-1 and endostatin in vitro and in vivo. A tumor bearing mouse model and an experimental lung metastasis model in animal experiments were used to explore the therapeutic effect of in vivo production of human TIMP-1 and endostatin after the implantation of primary fibroblasts infected with the indicated adenovirus into tumor-bearing mice and a cytochemical method was used to observe histopathological changes of the tumor. An experimental lung metastasis model was established by injecting B16BL6 cells into the tail vein of mice and adenovirus-infected primary fibroblasts were subcutaneously implanted into the mice 24 hours later. Twenty-one days after tumor cell injection, mice were sacrificed to examine the effect on nodules visible as black forms on the surface of the lungs in B16BL6 cells.Results TIMP-1 and endostatin were secreted into the supernatants of cultures of Ad-TIMP-1 and Ad-End-infected mouse primary fibroblasts. We also observed that implantation of fibroblasts infected with Ad-TIMP-1 alone, Ad-End alone, or Ad-TIMP-1 plus Ad-End resulted in detectable blood levels which may clearly inhibit the tumor growth and metastasis in a murine melanoma model.Conclusion These results suggest the high capacity of transfection for the delivery of TIMP-1 or endostatin gene constructs into primary fibroblasts, and demonstrate that the implantation of TIMP-1 and endostatin producing fibroblasts at a site in vivo where direct secretion of TIMP-1 and endostatin into the blood is possible represented a promising approach for the development of cancer therapy.     

Potent antitumor efficacy of an E1B 55 kDa-deficient adenovirus carrying murine endostatin in hepatocellular carcinoma

Data from clinical trails have shown that the antitumoral effect of ONYX-015, an E1B 55kDa-deficient adenovirus, as monotherapy is insufficient. To enhance its efficiency, CNHK200-mE, another E1B 55kDa-deficient adenovirus armed with a mouse endostatin gene was constructed and its antitumoral activities against hepatocellular carcinoma （HCC） in vitro and in vivo were investigated. The selective replication and cytotoxicity of CNHK200-mE in Hep3B and HepGII cells independent of p53 status were confirmed via TCID50 and 3-（4,5dimetylthiazol）-2,5-diphenyltetrazolium bromide （MTT） assays. Potent tumor growth suppression on SMMC-7721 xenografts in nude mice was observed and a synergistic effect of the carrier virus and the therapeutic gene was suggested. Moreover, in comparison with the nonreplicative adenovirus carrying the same therapeutic gene, amplified transgene expression of mouse endostatin in vitro and in vivo were confirmed by Western blotting and ELISA assay. The effective angiogenesis inhibition and replication of CNHK200-mE in nude mice xenografts were demonstrated by immunohistochemistry. In conclusion, the recombinant adenovirus CNHK200-mE is a replication-competent oncolytic virus mediating high expression of therapeutic gene. Because CNHK200-mE is capable of replicating in and lysing HCC cells selectively with effective tumor growth suppression and antiangiogenic activity on HCC xenografts in nude mice, it holds good potential for the treatment of HCC.     

Effects of nuclear translocation of tissue transglutaminase and the release of cytochrome C on hepatocyte apoptosis

Objective To assess the effects of nuclear translocation of tissue transglutaminase (TTG) and the release of cytochrome C on hepatocyte apoptosis and to reveal the mechanism of signal transcluction of early apoptosis in injured hepatocytes.Methods Hepatocytes isolated from tissue transglutaminase gene knock-out mice and rats were stimulated with ethanol. Proteins from whole cell, cytoplasm and nuclei were extracted for determination of TTG activity by ^14C-putrescine incorporation. Distribution of TTG throughout the entire cell, as well as just nucleus was observed under a confocal scanning microscope. The amount of cytochrome C released from mitochonclria was determined by ELISA. Cell apoptosis was observed by fluorescent cytochemistry.Results TTG activity in whole cells and nuclei was significantly increased after the hepatocytes were treated with ethanol. Cytochrome C release was remarkably increased in the cells isolated from rat and wild-type mouse after treatment with ethanol but not in TTG gene knock-out mice. Cellular apoptosis appeared in hepatocytes isolated from rats and wild-type mice but not in the hepatocytes from TTG gene knock-out mice after stimulation with ethanol.Conclusions Increased TTG in hepatocytes can be translocated into the nucleus and promote release of mitochonclrial cytochrome C into the cytoplasm. Passing through a series of signal pathways, hepatocyte apoptosis is induced eventually.     

Ursolic Acid Inhibits T-Cell Activation through Modulating Nuclear Factor-κB Signaling

<正>Objective:To investigate the effects of ursolic acid(UA) on T-cell proliferation and activation,as well as to examine its effect on nuclear factor-κB(NF-κB) signaling pathway in T cells.Methods:T-cells isolated from BALB/c mice were incubated with UA at concentrations ranging from 5-30μmol/L in the presence of phorbol 12-myristate 13-acetate(PMA) or PMA plus ionomycin.The proliferation of T cells was measured by the MTT assay.The expressions of CD69,CD25,and CD71 on T-cell surface were analyzed using flow cytometry. The level of interleukin-2(IL-2) in the culture supernatant of activated T cells was quantified by enzyme-linked immunosorbent assay(ELISA).The level of phosphorylated IκB-α(p-lκB-α) in total protein and p65,a subunit of NF-κB,nuclear translocation were measured by Western blot analysis.Results:UA in a dose-dependent manner significantly decreased the proliferation and inhibited the surface expressions of CD69,CD25,and CD71 in murine T lymphocytes upon in vitro activation(P0.01).Significant reduction of IL-2 production was found in activated T cells treated with UA(P0.01).The PMA-induced increase in p-lκB-αprotein was inhibited,and nuclear translocation of p65 from the cytoplasm was blocked by UA.Conclusion:UA is a potent inhibitor for T cell activation and proliferation;these effects are associated with the inhibition of NF-κB signaling pathway.     

PTA1配体表达的免疫组化研究

INTRODUCTION T lineage specific activation antigen 1 (TLiSA1), first reported by Burns in 1985[1], was renamed PTA1 in 1989 because of its expression on platelets as well[2]. Since 1985, a lot of investigations have been done on PTA1 expression, its functions and its relationship with diseases. PTA1, mainly expressed on activated T cells, platelets and megakaryocytes lineage, was involved in signal transduction of T cell activation and differentiation as well as platelet activation and aggregation. PTA1 mAb (Leo-A1) was found to stimulate activation and aggregation of platelets and inhibit differentiation of CTL.     

Expression of recombination-activating genes and T cell receptor gene recombination in the human T cell leukemia cell line

Background Recent studies have suggested that mature T cells can change their specificity through reexpression of recombination-activating genes （RAG） and RAG-mediated V（D）J recombination. This process is named receptor revision and has been observed in mature peripheral T cells from transgenic mice and human donors. However, whether the receptor revision in mature T cells is a random or orientated process remains poorly understood. Here we used the Jurkat human T cell line, which represents a mature stage of T cell development, as a model to investigate the regulation of T cell receptor （TCR） gene recombination. Methods TCR Dβ-Jβ signal joint T cell receptor excision DNA circles （sjTRECs） were determined by nested and seminested PCR. Double-strand DNA breaks at recombination signal sequences （RSSs） in the TCRVβ chain locus were detected by ligation-mediated-PCR. Further analysis of the complementarity-determining region 3 （CDR3） size of the TCRVβ chain was examined by the TCR GeneScan technique. Results RAG1, RAG2, and three crucial components of the nonhomologous DNA end-joining （NHEJ） pathway were readily detected in Jurkat. Characteristics of junctional diversity of Dβ2-Jβ2 signal joints and ds RSS breaks associated with the Dβ2 5＇ and Dβ 2 3＇ sites were detected in DNA from Jurkat cells. CDR3 size and the gene sequences of the TCRVβ chain did not change during cell proliferation. Conclusions RAG1 and RAG2 and ongoing TCR gene recombination are coexpressed in Jurkat cells, but the ongoing recombination process may not play a role in modification of the TCR repertoire.However, the results suggest that Jurkat could be used as a model for studying the regulation of RAGs and V（D）J recombination and as a ＂special＂ model of the coexistence of TCR gene rearrangements and ＂negative＂ receptor revision.     

Expression of CⅡTA Gene in Five Human Malignant Hematological Cell Lines and Its Significance

The role of MHC class Ⅱ transactivator (CⅡTA) in constitutive or IFN-γ inducib|e expression of HLA molecules in human malignant hematological cell lines was investigated. The expression of HLA molecules and CⅡTA protein was detected by Western blot, immunohistochemistry and flow cytometry. The expression of CⅡTA gene was determined by RT-PCR. The capability of peripheral blood T cell reaction stimulated by tumor cells was monitored by mixed lymphocyte reaction. It was found that the HLA Ⅱ-positive tumor cells expressed the CⅡTA quite well, andthe expression of HLA Ⅰ＋Ⅱ was increased in the tumor cells with constitutive or inducible expression of CⅡTA after induced by IFN-γ. The tumor cells which did not express CⅡTA after in-duced by IFN-γ were not response to the expression of HLA Ⅱ promoted by IFN-γ. It suggests a correlation between the inability of some malignant hematological cell lines in response to IFN-γ for HLA expression and the deficiency in the inducible expression of CⅡTA, indicating CⅡTA might take part in the regu|ation of HLA Ⅰ＋Ⅱ expression in the tumor cells, which might p|ay an important role in tumor immunologic escape.     

Moxibustion Promotes Formation of Granulation in Wound Healing Process through Induction of Transforming Growth Factor-β in Rats

Objective: To examine the effect of moxibustion on the wound healing process and its mechanism using a rat wound model. Methods: Sixty male Sprague-Dawley rats were randomly divided into a sham-treated group(n=30, wound surgery only) and a moxibustion group(n=30, wound treated with moxibustion). Circular fullthickness skin wounds were produced in rats. Moxibustion was applied to the edge of wound and was continued on alternating days till 14 days after surgery, followed by measurement of wound size. Expression of collagens, prolyl-4-hydroxylase(P4 H) and transforming growth factor-β(TGF-β) were evaluated by histochemical study and real-time polymerase chain reaction. Results: The size of the wound lesion was significantly reduced in rats treated with moxibustion as compared to that in sham-treated rats at 4–10 days after wounding(P0.01). Moxibustion stimulated mRNA expression of collagens at 4 days(P0.01), but not at 7 days, accompanied by enhanced proliferation of P4 H-positive fibroblasts. Of importance, expression of TGF-β in tissue from the wound lesion treated with moxibustion was significantly increased as compared to that in sham-treated rats at 4 days(P0.01 or P0.05), but not at 7 days. Conclusions: The treatment with moxibustion promoted the wound healing process in the early phase through proliferation of fibroblasts and rapid formation of granulation, possibly mediated by induction of TGF-β which is a key molecule in the physiological process of wound healing. Moxibustion can be expected to be effective as complementary treatment for intractable ulcers.     

Expression of monocyte chemoattractant protein-1 in the pancreas of mice

Background Type 1 diabetes has been recognized as an organ specific autoimmune disease owing to the immune destruction of pancreatic islet β cells in genetically susceptible individuals. In both human and rodent models of type 1 diabetes, such as nonobese diabetic (NOD) mice, biobreeding rats, the disease has a distinct stage characterized by immune cells infiltrating in the pancreas (insulitis). The major populations of infiltrating cells are macrophages and T lymphocytes. Therefore, immune cell infiltration of pancreatic islets may be a crucial step in the pathogenesis of type 1 diabetes. Monocyte chemoattractant protein-1 can specifically attract monocytes in vivo. Interferon induced protein-10 has chemoattractant effects on the activated lymphocytes. In this study, we analysed the expression of monocyte chemoattractant protein-1 in the pancreas of mice and interferon inducible protein-10 mRNA in the pancreas of NOD mice, and discussed their possible role in the pathogenesis of type 1 diabetes. Methods The immunohistochemical method and immunoelectronmicroscopy were used to evaluate the expression of monocyte chemoattractant protein-1 in the pancreas of NOD mice and BALB/c mice. RT-PCR was used to evaluate the expression of monocyte chemoattractant protein-1 and interferon inducible protein mRNA in NOD mice.Results Monocyte chemoattractant protein-1 was positive in the pancreas of NOD mice, whereas negative in the pancreas of BALB/C mice. RT-PCR showed that monocyte chemoattractant protein-1 and interferon inducible protein-10 mRNA could be found in the pancreas of NOD mice. Immunoelectronmicroscopy demonstrated that monocyte chemoattractant protein-1 was produced by β cells and stored in the cytoplasm of the cells.Conclusions Pancreatic islet β cells produce monocyte chemoattractantprotein-1 in NOD mice. Monocyte chemoattractant protein-1 may play an important part in the pathogenesis of type 1 diabetes by attracting monocytes/macrophages to infiltrate pancreatic islets.     

Treatment of experimental Coxsackie B-3 viral myocarditis with Astragalus membranaceus in mice.

A murine model system for observing the effect of Astragalus Membranaceus (AM) on experimental myocarditis caused by Coxsackie B-3 virus (CB3V) was developed in 4-week-old male BALB/C mice. Gross, histopathologic and ultrastructural examinations of the infected-AM treated group showed that the severity and involved area of the myocardial lesions became milder and smaller than those in the infected-NS treated mice. The total lesion area, and the total lesion area/total myocardial area examined (%) and virus titer in the former group were also smaller and lower than those in the latter group. The results suggest that AM is effective in the inhibition of Coxsackie B virus propagation and protection of myocardium in mouse myocarditis.