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To investigate the roles of tumor necrosis factor (TNF) and lymphotoxin (LT)-alpha in the development and function of the immune system, the Tnf and Ltalpha genes were simultaneously inactivated in mice by homologous recombination. These mutant mice are highly susceptible to Listeria monocytogenes infection and resistant to endotoxic shock induced by the(More)
Cyclophilin (CYP) is the major intracellular binding protein for the immunosuppressive drug cyclosporine (CS). CYP distribution was investigated in human tissues by solid-phase immunoassay, Western and Northern blot analysis as well as immunohistochemistry. CYP was found in all tissues examined at concentrations in the range of 1 microgram/mg protein.(More)
Induction of growth inhibition in human colorectal carcinoma cell lines by interleukin (IL)-4 and IL-13 was associated with the neophosphorylation of a 170 kDa cellular protein, identified as insulin receptor substrate-1 (IRS-1) by immunoprecipitation. Tyrosine phosphorylation of IRS-I was also induced by insulin and insulin-like growth factor I. Sublines(More)
Interleukin 12 (IL-12) activates natural killer (NK) and T cells with the secondary synthesis and release of interferon-gamma (IFN-gamma) and other cytokines. IL-12-induced organ alterations are reported for mice and the pathogenetic role of IFN-gamma is investigated by the use of mice deficient in the IFN-gamma receptor (IFN-gamma R-/-). IL-12 caused a(More)
The ability of cytokine synthesis inhibitory factor or interleukin-10 (IL-10) and interferon-gamma (IFN-gamma) to modulate the production of tumor necrosis factor (TNF-alpha) induced by lipopolysaccharide (LPS) was examined in mouse bone marrow-derived macrophages (BMDM). IFN-gamma profoundly enhances LPS-stimulated TNF-alpha production, whereas IL-10 is(More)
The immunosuppressive macrolide rapamycin inhibits cytokine-driven proliferation of lymphocytes, acting at a later stage of T lymphocyte activation than the related compound FK506 or cyclosporin, which block IL-2 transcription. However, the effect of rapamycin on the expression of the IL-2 receptor alpha-chain (CD25) is less well documented. This study has(More)
Although cyclosporine has high specificity for the immune system, immunosuppressive therapy with CsA is often complicated by nephrotoxicity. The main morphologic targets of CsA nephrotoxicity include the tubular epithelial and endothelial cells. These cells were investigated in vitro. CsA caused a dose- and time-dependent inhibition of cell growth,(More)
Interleukin 4 (IL4) produced by activated T cells expresses its biological effects on T and B lymphocytes by binding to specific membrane receptors. Cross-linking of human recombinant 125I-IL4 to peripheral blood mononuclear cells identifies a trimolecular complex consisting of a 65/70-kDa doublet and a 110-kDa protein. Scatchard analysis reveals about 300(More)
The immunosuppressant cyclosporine A (CSA) has been shown to bind to the ubiquitous cellular protein, cyclophilin, and to inhibit its rotamase activity. In the present study, 3H-cyclosporine diazirine analogue was used to photolabel viable human cells of lymphoid and fibroblast origin in order to identify the intracellular targets for the drug. While(More)
The effect of the immunosuppressant cyclosporin (CsA) on the expression of interleukin (IL) 4 membrane receptors on human peripheral blood mononuclear cells (PBMC) was investigated after cell activation by anti-CD3 antibody, IL 2 or IL 4. Previous studies with 125I-labeled IL 4 identified on resting lymphocytes a trimolecular complex consisting of a(More)