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Weaker Expression (weaker + expression)
Selected AbstractsHeterogeneity of Kir4.1 channel expression in glia revealed by mouse transgenesisGLIA, Issue 16 2009Xiaofang Tang Abstract The weakly inwardly rectifying K+ channel Kir4.1 is found in many glial cells including astrocytes. However, questions remain regarding the relative contribution of Kir4.1 to the resting K+ conductance of mature astrocytes in situ. We employed a bacterial artificial chromosome transgenic approach in mice to visualize Kir4.1 expression in vivo. These mice (Kir4.1-EGFP) express enhanced green fluorescent protein (EGFP) under the transcriptional control of the Kir4.1 promoter. The brains of adult Kir4.1-EGFP transgenic mice showed co-expression of EGFP and Kir4.1 in astrocytes. In addition, weaker expression of EGFP was detected in NG2+ glial cells when compared with EGFP expression in GFAP+ glial cells. Whole-cell voltage clamp recordings of EGFP+ glial cells in the CA1 area of the adult mouse hippocampus indicated astrocytes displaying properties consistent with both the "passive" and "complex" subpopulations. EGFP+ cells with bright fluorescence had the linear current,voltage (I,V) relationships and extensive gap junctional coupling characteristic of passive astrocytes. However, EGFP+ glia with weaker fluorescence displayed properties associated with complex astrocytes including nonlinear I,V relationships and lack of intercellular gap junctional coupling. Pharmacological blockade of inward currents implied that Kir4.1 channels constitute the dominant resting K+ conductance in both glial cell types and are more highly expressed in passive astrocytes. These results suggest differential expression of Kir4.1 in glia and that this channel likely underlies the resting K+ conductance in passive and complex astrocytes. © 2009 Wiley-Liss, Inc. [source] The lectin-like domain of thrombomodulin interferes with complement activation and protects against arthritisJOURNAL OF THROMBOSIS AND HAEMOSTASIS, Issue 8 2006M. VAN DE WOUWER Summary.,Background: Thrombomodulin (TM) is predominantly a vascular endothelial cell plasma membrane glycoprotein that, via distinct structural domains, interacts with multiple ligands, thereby modulating coagulation, fibrinolysis, complement activation, inflammation and cell proliferation. We previously reported that by mediating signals that interfere with mitogen-activated protein kinase and nuclear factor ,B pathways, the amino-terminal C-type lectin-like domain of TM has direct anti-inflammatory properties. Methods: In the current study, we use murine models of acute inflammatory arthritis and biochemical approaches to assess the mechanism by which the lectin-like domain of TM modifies disease progression. Results: Mice lacking the lectin-like domain of TM (TMLeD/LeDmice) develop inflammatory arthritis that is more rapid in onset and more severe than that developed in their wildtype counterparts. In two models of arthritis, treatment of mice with recombinant soluble lectin-like domain of TM significantly suppresses clinical evidence of disease and diminishes monocyte/macrophage infiltration into the synovium, with weaker expression of the pro-inflammatory high mobility group box chromosomal protein 1. While thrombin-TM mediated activation of thrombin activatable fibrinolysis inhibitor inactivates complement factors C3a and C5a, we show that TM has a second independent mechanism to regulate complement: the lectin-like domain of TM directly interferes with complement activation via the classical and lectin pathways. Conclusions: These data extend previous insights into the mechanisms by which TM modulates innate immunity, and highlight its potential as a therapeutic target for inflammatory diseases. [source] Ability of low-molecular-weight heparin to alleviate proteinuria by inhibiting respiratory syncytial virus infectionNEPHROLOGY, Issue 7 2008YANNAN GUO SUMMARY: Aim: Low-molecular-weight heparin (LMWH) is a negatively charged glycoprotein and has a very similar structure to that of cell surface heparin sulfate (HS). Thus, LMWH, an analog of HS, may inhibit positively charged respiratory syncytial virus (RSV) infection through cooperative electrostatic association. Methods: In this study, rats were respectively treated with 400 IU/kg LMWH before, during or after being inoculated with 6 × 106 plaque-forming unit (PFU) RSV. RSV and normal control groups were respectively inoculated by RSV and virus-free Dulbecco's modified Eagle's medium (DMEM). HeLa cells in vitro were pretreated with LMWH, elastase (ELA), heparinase (HpaIII) and protamine before being inoculated with 6 × 101 PFU RSV. RSV infectivity was determined by in situ hybridization and plaque assay. Results: After inoculation, the urinary protein excretion and serum parameters in LMWH-treated rats were significantly lower than those in the RSV group. No abnormalities of glomerular structure were observed in LMWH-treated groups whereas swelling and slight hypercellularity in minority glomeruli and foot process effacement were observed in the RSV group. RSV RNA of LMWH-treated rats had weaker expression than that of the RSV group. In vitro, RSV infection in RSV + LMWH, HpaIII + ELAI, protamine + ELAI, ELAI, HpaIII and protamine treatment cells were significantly lower than that of the RSV control, and that in RSV + LMWH was the least. There were no significant differences in RSV infection between ELAI + LMWH and RSV control. Conclusion: Our study confirmed that there is a correlation between RSV and proteinuria in rats. LMWH can alleviate proteinuria in rats through inhibiting RSV from binding with HS which plays an important role in the onset of RSV infection. [source] C-C chemokine receptor 2 (CCR2) deficiency improves bleomycin-induced pulmonary fibrosis by attenuation of both macrophage infiltration and production of macrophage-derived matrix metalloproteinasesTHE JOURNAL OF PATHOLOGY, Issue 5 2004Toshiyuki Okuma Abstract Macrophage infiltration is implicated in various types of pulmonary fibrosis. One important pathogenetic process associated with pulmonary fibrosis is injury to basement membranes by matrix metalloproteinases (MMPs) that are produced mainly by macrophages. In this study, C-C chemokine receptor 2-deficient (CCR2,/,) mice were used to explore the relationship between macrophage infiltration and MMP activity in the pathogenesis of pulmonary fibrosis, using the bleomycin-induced model of this disease process. CCR2 is the main (if not only) receptor for monocyte chemoattractant protein-1/C-C chemokine ligand 2 (MCP-1/CCL2), which is a critical mediator of macrophage trafficking, and CCR2 ,/, mice demonstrate defective macrophage migration. Pulmonary fibrosis was induced in CCR2,/, and wild-type (CCR2+/+) mice by intratracheal instillation of bleomycin. No significant differences in the total protein concentration in bronchoalveolar lavage (BAL) fluid, or in the degree of histological lung inflammation, were observed in the two groups until day 7. Between days 3 and 21, however, BAL fluid from CCR2,/, mice contained fewer macrophages than BAL fluid from CCR2+/+ mice. Gelatin zymography of BAL fluid and in situ zymography revealed reduced gelatinolytic activity in CCR2,/, mice. Immunocytochemical staining showed weaker expression of MMP-2 and MMP-9 in macrophages in BAL fluid from CCR2,/, mice at day 3. Gelatin zymography of protein extracted from alveolar macrophages showed reduced gelatinolytic activity of MMP-2 and MMP-9 in CCR2,/, mice. At days 14 and 21, lung remodelling and the hydroxyproline content of lung tissues were significantly reduced in CCR2,/, mice. These results suggest that the CCL2/CCR2 functional pathway is involved in the pathogenesis of bleomycin-induced pulmonary fibrosis and that CCR2 deficiency may improve the outcome of this disease by regulating macrophage infiltration and macrophage-derived MMP-2 and MMP-9 production. Copyright © 2004 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd. [source] Molecular characterization and expression analysis of BmNOX in two strains of Bombyx mori with contrasting viral resistance phenotypeARCHIVES OF INSECT BIOCHEMISTRY AND PHYSIOLOGY (ELECTRONIC), Issue 3 2010Ruchita Selot We recently documented the identification of a 26.5,kDa protein named BmNox in the gut fluid of Nistari strain of Bombyx mori, which possessed antiviral activity against BmNPV in vitro. In this report, we report the characterization of the full-length gene encoding BmNOX and the levels of expression of this gene in select tissues of silkworm larvae from a BmNPV-susceptible and a BmNPV-resistant strain to the defense capability in Bombyx mori larvae challenged with BmNPV. We also evaluated the BmNox expression in various stages of larval life of a resistant and a susceptible strain of Bombyx mori selected from among a panel of strains of silkworm. Nistari, a multivoltine strain of silkworm, expressed BmNOX during all five larval stages, and were highly resistant to BmNPV infection. In sharp contrast, CSR2, a bivoltine strain, showed weaker expression of BmNOX in the anterior midgut in larval life and was highly susceptible to BmNPV infection. BmNOX is a secretory protein with dual expression in gut fluid and mid gut tissue. BmNOX is expressed heavily in the posterior mid gut, with weaker expression in the fore- and mid-gut regions. © 2010 Wiley Periodicals, Inc. [source] | ||||||||||