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Transendothelial migration of monocytes followed by their differentiation into macrophages involves interaction of monocytes
with subendothelial matrix. The influence of extracellular matrix on monocyte–macrophage differentiation was studied using
an in vitro model system with human PBMC maintained on different matrix protein substrata. Upregulation of macrophage specific marker
activities such as endocytosis of modified proteins, changes in expression of cell surface antigen, and production of matrix
metalloproteinases was studied. Cells maintained on Fibronectin (Fn) showed significantly higher rate of endocytosis and production
of MMP2 and MMP9 when compared to other matrix protein substrata. Immunoblot analysis, ELISA, and zymography showed that Fn-dependent
upregulation of MMPs was blocked by antibodies to α5β1 integrin indicating that the Fn effect was mediated by integrins. The Fn effect on mo–mΦ was blocked by genistein and herbimycin.
As monocytes differentiate to macrophages there was an increase in the rate of production of Fn. These results indicate the
influence of the microenvironment of the cell, particularly Fn, on mo–mΦ differentiation and integrin-mediated downstream
signaling through focal adhesion kinase and Src type tyrosine kinase is involved in this. 相似文献
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Hu LY Lei HJ Du D Johnson TR Fedij V Kostlan C Yue WS Lovdahl M Li JJ Carroll M Dettling D Asbill J Fan C Wade K Pocalyko D Lapham K Yalamanchili R Samas B Vrieze D Ciotti S Krieger-Burke T Sliskovic D Welgus H 《Bioorganic & medicinal chemistry letters》2007,17(20):5693-5697
A series of amino-pyridines were synthesized and evaluated for androgen antagonist activities. Among these compounds, (R)-(+)-6-[methyl-(1-phenyl-ethyl)-amino]-4-trifluoromethyl-nicotinonitrile was the most active example of this class. This compound displayed potent androgen receptor antagonist activity as well as favorable pharmacokinetic characteristics for a potential topical agent. It also demonstrated remarkable potency for stimulating hair growth in a male C3H mouse model as well as reducing sebum production in the male Syrian hamster ear model. 相似文献
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Karlo D. T. Natividad Simon R. Junankar Norhanani Mohd Redzwan Radhika Nair Rushika C. Wirasinha Cecile King Robert Brink Alexander Swarbrick Marcel Batten 《PloS one》2013,8(3)
Interleukin-27 (IL-27) is a pleiotropic cytokine but its immunosuppressive effects predominate during many in vivo immunological challenges. Despite this, evidence from tumor cell line transfer models suggested that IL-27 could promote immune responses in the tumor context. However, the role of IL-27 in immunity against tumors that develop in situ and in tumor immunosurveillance remain undefined. In this study, we demonstrate that tumor development and growth are accelerated in IL-27 receptor α (Il27ra)-deficient mice. Enhanced tumor growth in both carcinogen-induced fibrosarcoma and oncogene-driven mammary carcinoma was associated with decreased interferon-γ production by CD4 and CD8 T cells and increased numbers of regulatory T-cells (Treg). This is the first study to show that IL-27 promotes protective immune responses against endogenous tumors, which is critical as the basis for future development of an IL-27 based therapeutic agent. 相似文献
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Prasanthi Malapati Vagolu Siva Krishna Radhika Nallangi Nikhila Meda Rudraraju Reshma Srilakshmi Dharmarajan Sriram 《Bioorganic & medicinal chemistry》2018,26(1):177-190
Mycobacterium tuberculosis glutamate racemase is an essential enzyme involved in peptidoglycan synthesis and conserved in most bacteria. Small molecule inhibitors were reported on other bacterial species whereas in M. tuberculosis it wasn’t explored much. In this study we have screened in house compound library using fluorescence thermal shift assay and enzyme inhibition assay, form this (1-(3-(benzo[d]thiazol-2-yl)phenyl)-3-(p-tolyl)thiourea) was identified as lead compound with IC50 19.47?±?0.81?μM. Further lead optimization by synthesis resulted in twenty-three compounds, of which Compound 25?has shown more efficacy compared to lead 1 showing non-competitive mode of inhibition with IC50 1.32?±?0.43?μM. It also showed significant activity (represented in log reduction) in nutrient starved dormant M. tuberculosis model (2.1), M. tuberculosis biofilm assay (2.0) and in vivo M. marinum infected zebrafish model (3.5). 相似文献