Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:3.1.6.12 (chondroitinase)
 2,183 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The amino acid sequence of interferon gamma (IFN-gamma) has basic amino acid clusters similar to the heparin-binding consensus sequences found in other proteins that bind to proteoglycans (PGs). We investigated whether recombinant human IFN-gamma could bind to extracellular matrix (ECM) PGs secreted by human arterial smooth muscle cells (HASMCs) in vitro and whether the interaction affected the cellular response to IFN-gamma. As an in vitro model of ECM we used the basement membrane from HASMCs in culture. The binding of 125I-IFN-gamma to ECM was reduced significantly by pretreatment of ECM with chondroitinase ABC, an enzyme that degrades chondroitin-sulfate glycosaminoglycans. IFN-gamma binding to ECM was reduced by increasing concentrations of chondroitin-6-sulfate. 125I-IFN-gamma (0.05 to 2 ng/mL) binding data indicated an apparent Kd of 2 x 10(-11) mol/L and a maximum binding of 1.6 x 10(6) IFN-gamma molecules bound per square millimeter of ECM. Experiments with synthetic peptides suggested that residues 127 through 135 (AKTGKRKRS) are involved in the binding. The binding to chondroitin-sulfate PGs was confirmed by affinity chromatography of isolated [35S]chondroitin-sulfate PGs from ECM and cell-culture medium on immobilized IFN-gamma. The binding was abolished by treatment with chondroitinase ABC. ECM-bound IFN-gamma was more effective in inducing the expression of class II major histocompatibility antigens such as HLA-DR in HASMCs and human arterial endothelial cells than soluble IFN-gamma. These results suggest a role for chondroitin-sulfate PGs in immobilizing IFN-gamma in the ECM compartment and enhancing the cellular response to IFN-gamma.
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PMID:Interferon gamma binds to extracellular matrix chondroitin-sulfate proteoglycans, thus enhancing its cellular response. 767 Sep 61

Eosinophils, prominent cells in asthmatic inflammation, have been shown to synthesize, store, and release an array of up to 18 cytokines and growth factors, including interleukin-6 (IL-6). In this report, we show that IL-6 immunofluorescence localizes to the matrix of the crystalloid granule in peripheral blood eosinophils from atopic asthmatics using confocal laser scanning microscopy (CLSM). Granule localization of IL-6 was confirmed using dot-blot analysis and enzyme-linked immunosorbent assay (ELISA) on subcellular fractions of highly purified eosinophils produced from density centrifugation across a 0% to 45% Nycodenz gradient. IL-6 was found to coelute with eosinophil crystalloid granule marker proteins, including eosinophil peroxidase (EPO), major basic protein (MBP), arylsulfatase B, and beta-hexosaminidase. Immunoreactivity to IL-6 colocalized with granule-associated IL-2 and IL-5 in subfractionated eosinophils. We also made the novel and compelling observation that interferon gamma (IFNgamma), a Th1-type cytokine, stimulated an early elevation in eosinophil IL-6 immunoreactivity. A 2.5-fold enhancement of IL-6 immunoreactivity in eosinophil granules was observed within 10 minutes of IFNgamma treatment (500 U/mL), as determined by subcellular fractionation and CLSM. These findings suggest that IFNgamma has short-term effects on human eosinophil function and imply that a physiologic role exists for Th1-type cytokine modulation of Th2-type responses in these cells.
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PMID:Intracellular localization of interleukin-6 in eosinophils from atopic asthmatics and effects of interferon gamma. 951 52