Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0409974 (lupus)
 22,386 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The expression and tissue distribution of intercellular adhesion molecule-1 (ICAM-1) in skin biopsies from 12 patients with systemic (SSc) and localized (LS) scleroderma was studied and compared to the biopsies from patients with lupus erythematosus (LE) and normal individuals. In normal human skin ICAM-1 expression was restricted to the vascular endothelium, infiltrating mononuclear cells (MNC), and to few individual keratinocytes. In the inflammatory stage of SSc, however, the expression of ICAM-1 was dramatically increased at the site of MNC infiltrates and could also be detected on fibroblast-like cells lying well apart from these infiltrates in the deep dermis. In contrast, in LS ICAM-1 was expressed mainly at the sites of MNC infiltrates. In LE ICAM-1 expression was confined to the keratinocytes, endothelial cells, and mononuclear cells in the upper parts of the dermis. Analysis of serial tissue sections from patients with SSc demonstrated also colocalization of staining of ICAM-1 around blood vessels with LFA-1-positive lymphocytes. Increased expression of ICAM-1 in the dermis of patients with SSc may represent an important mechanism by which MNC become localized and retained at a site of connective tissue inflammation, leading to the activation of fibroblasts.
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PMID:Expression of intercellular adhesion molecule-1 (ICAM-1) in the skin of patients with systemic scleroderma. 168 92

Interactions of the ligand/receptor pair LFA-1(CD11a/CD18) and ICAM-1(CD54) initiate and control the cell-cell interactions of leukocytes and interactions of leukocytes with parenchymal cells in all phases of the immune response. Induction of the intercellular adhesion molecule 1 (ICAM-1) on the surface of epidermal keratinocytes has been proposed as an important regulator of contact-dependent aspects of cutaneous inflammation. Ultraviolet radiation (UVR) also modifies cutaneous inflammation, producing both up- and down-regulation of contact hypersensitivity. We have found that UVR has a biphasic effect on the induction of keratinocyte CD54. Using immunofluorescence and FACS techniques to quantitate cell-surface CD54 staining, we have shown that UVR (100 mJ/cm2 of UVB) significantly (p less than 0.01) inhibits keratinocyte CD54 induction by gamma interferon 24 h after irradiation. However, at 48, 72, and 96 h after UVR (10 to 100 mJ/cm2), CD54 expression is significantly induced (p less than 0.01 to p less than 0.001) to levels even greater than are induced by gamma interferon (20 U/ml). In addition, at 48, 72, or 96 h following UVR (30-100 mJ/cm2), the gamma-interferon-induced CD54 expression on human keratinocytes is also strongly (p less than 0.05 to p less than 0.001) enhanced. In this cell-culture system, gamma interferon and TNF-alpha are both strong CD54 inducers and are synergistic, but GM-CSF, TFG-beta, and IL-1 have no direct CD54-inducing effects. Thus the effects of UVR on CD54 induction are biphasic, producing inhibition at 24 h and induction at 48, 72, and 96 h. This effect on CD54 may contribute to the biphasic effects of UVR on delayed hypersensitivity in vivo. The early inhibition of ICAM-1 by UVR may also contribute to the therapeutic effects of UVR. We also speculate that the late induction of ICAM-1 by UVR might be an important step in the induction of photosensitive diseases such as lupus erythematosus.
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PMID:Ultraviolet radiation can either suppress or induce expression of intercellular adhesion molecule 1 (ICAM-1) on the surface of cultured human keratinocytes. 197 76

Immunologic cytotoxicity is an important endpoint of the immune response to tumors, viral infected cells, grafted tissues, and exogenous microorganisms, and is also an important mechanism of disease, especially in autoimmunity. There are multiple mechanisms of immunologic cytotoxicity, but each has three major stages: leukocyte/target attachment, specific recognition, and target lysis following effector activation. Adhesion molecules present on leukocytes and potential targets appear to be involved in all three stages of cytotoxicity. A major factor in all types of cellular cytotoxicity is the interaction of LFA-1 on leukocytes and CAM-1 on targets. Modulation of ICAM-1 levels on target by the cytokines TFN-g, IL-1, and TNF-a is a major point of control of the susceptibility of targets to cytotoxicity by many different cytotoxic mechanisms. It also appears that modulation of the avidity of LFA/ICAM-1 binding is another important control point in modulating immunologic cytotoxicity. Cytokines also have important effects on immunologic cytotoxicity in ways other than adhesion molecule induction: effector priming to better respond to specific recognition signals, effector mobilization into tissue, and expansion of cytotoxic effector populations. ICAM-1 on the surface of epidermal keratinocytes and melanocytes is likely to greatly influence cytotoxic damage of these cells in diseases as photosensitive lupus erythematosus, lichen planus, erythema multiforme, and vitiligo. It has been found that the epidermal staining pattern for ICAM-1 in each of these diseases in distinctive and different in each disease. It is proposed that disease-specific induction of ICAM-1 by factors such as UVR and herpes-virus is an important determinant in triggering these skin diseases and in determining the pattern of disease.
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PMID:Cytokine modulation of adhesion molecules in the regulation of immunologic cytotoxicity of epidermal targets. 225 27

Cultured human keratinocytes were lysed by activated PBMC in a 4-h 51Cr release assay. PBMC were activated by incubation with 50 U/ml of rIL-2 for 4 days. The cytotoxic precursors were found to be NKH1+ and included both CD2+ and CD2- phenotypes. This cytotoxicity was not genetically restricted, as cells killed both allogeneic and autologous keratinocytes without priming. Cytotoxicity was blocked by pre-incubation of effector cells with mAb against LFA-1 alpha-(TS1/22) and beta-chains (TS1/18), but not by antibodies directed against CD4, CD8, or leukocyte common Ag (T200) suggesting that LFA-1 is an important interactive molecule in this cytotoxicity. IFN-gamma is reported to upregulate ICAM-1, the ligand for LFA-1. Pre-treatment of target keratinocytes with IFN-gamma was also found to greatly increase the sensitivity of keratinocytes to lysis. This increased sensitivity to lysis was blocked by anti-LFA-1 and anti-ICAM-1, but not by anti-DR (L243), and thus was not the result of increased DR expression. Such treated targets were lysed at low levels (15 to 18%) by an Ag-specific CD8+ cytotoxic clone as well as a T cell line derived from a skin lesion of allergic contact dermatitis. In contrast, control keratinocytes were only sensitive to IL-2-activated PBMC as described above. The above findings may be relevant to a variety of conditions in which epidermal damage is associated with lymphocytic infiltrate. These conditions include graft-vs-host disease, erythema multiforme, and lupus erythematosus. DR+ keratinocytes, which may be a marker for IFN-gamma are also found in the above conditions. It is suggested that epidermal pathology may be mediated by non-specific cytotoxicity induced in the course of an immune response.
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PMID:Non-specifically activated human peripheral blood mononuclear cells are cytotoxic for human keratinocytes in vitro. 246 92

Treating activated CD4+ T cells with DNA methyltransferase inhibitors modifies gene expression and induces autoreactivity. Adoptive transfer of viable polyclonal autoreactive cells causes a lupus-like disease, most likely because of one or more effector functions expressed by the autoreactive cells. However, the number of potential effector mechanisms expressed by polyclonal cells is large. To more readily identify responsible mechanisms, we asked if autoimmunity can be induced by using the conalbumin-reactive, cloned Th2 cell line D10.G4.1, treated with 5-azacytidine (5-azaC) or procainamide (Pca). Treated, but not untreated, cells responded to syngeneic APCs without Ag, overexpressed LFA-1, spontaneously lysed syngeneic macrophages, and secreted relatively large amounts of IL-6, small amounts of IL-4, and no detectable IL-2 nor IFN-gamma. Adoptive transfer of treated, but not untreated, cells induced a severe immune complex glomerulonephritis, pulmonary alveolitis, central nervous system abnormalities including fibrinoid necrosis, karyorrhexis, and meningitis, and bile duct proliferation with periportal inflammatory cell infiltration resembling primary biliary cirrhosis. Anti-ssDNA, anti-dsDNA, and anti-histone Abs were also found. These experiments demonstrate that modification of this cloned T cell line with DNA methyltransferase inhibitors is sufficient to cause an autoimmune disease, with features of lupus as well as autoimmune liver disease. The results also raise the possibility that macrophage lysis, IL-6 secretion, and LFA-1 overexpression could contribute to the disease process. This system may be useful in testing the role of these and other pathologic mechanisms in the development of specific autoimmune lesions.
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PMID:Mechanism of drug-induced lupus. I. Cloned Th2 cells modified with DNA methylation inhibitors in vitro cause autoimmunity in vivo. 753 91

Current theories postulate that exposure to certain environmental agents will induce lupus in genetically predisposed individuals. However, the mechanisms by which environmental agents interact with the immune system to trigger lupus is unclear. Recent work has shown that some environmental agents associated with lupus, such as procainamide, hydralazine and ultraviolet light, will inhibit T cell DNA methylation, increase LFA-1 expression and induce autoreactivity. In addition, T cells isolated from patients with active lupus have hypomethlated DNA, diminished DNA methyltransferase activity and overexpress LFA-1 on an autoreactive subset of cells which spontaneously lyses autologous macrophages. More recent work has shown that the adoptive transfer of murine T cells made autoreactive with DNA methylation inhibitors is sufficient to cause a lupus-like disease in otherwise healthy syngeneic recipients. Together, these results support a new model of autoimmunity, in which certain environmental agents modify T cells by inhibiting DNA methylation and altering expression of certain genes, thereby inducing autoreactivity. The autoreactive cells then interact with the host to produce a lupus-like disease.
Lupus 1994 Dec
PMID:Role of T cell DNA methylation in lupus syndromes. 753 21

An immunohistochemical analysis of skin biopsies was performed in 18 patients with cutaneous lupus erythematosus (LE), using the alkaline phosphatase and monoclonal anti-alkaline phosphatase method (APAAP). The study group was subdivided on the basis of clinical criteria into 10 patients with chronic discoid LE (CDLE) and eight patients with subacute cutaneous LE (SCLE). Using a panel of monoclonal antibodies the following results were obtained: (i) ICAM-1 was expressed on epidermal keratinocytes, dermal inflammatory cells, and endothelial cells in most biopsies, whereas LFA-1 was confined to the dermis. Attachments between keratinocytes or endothelial cells and activated T lymphocytes via ICAM-1/LFA-1 may be a possible mechanism of target/effector recognition in cutaneous LE. (ii) HLA-DR was expressed on epidermal keratinocytes and cells of the dermal infiltrate, but not on endothelial cells. HLA-DR+ cells probably function as antigen-presenting cells, leading to major histocompatibility complex-restricted cellular cytotoxicity in cutaneous LE. (iii) Interleukin 2 receptor expression on dermal inflammatory cells was weak, indicating non-specific activation of T lymphocytes. (iv) The dermal inflammatory cells were T lymphocytes, mainly of the helper/inducer subtype. B lymphocytes were rarely found in the dermis. In general, no significant immunohistochemical differences were found between CDLE and SCLE, suggesting that these variants represent clinical subtypes rather than different pathogenetic entities.
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PMID:Immunohistochemical analysis of chronic discoid and subacute cutaneous lupus erythematosus--relation to immunopathological mechanisms. 775 49

The injection of (C57BL/6 x BALB/c)F1 spleen cells into newborn BALB/c mice results in the induction of a specific cytotoxic T lymphocyte (CTL) tolerance to the alloantigens. On the contrary, alloreactive CD4+ T cells persist in the host and are still able to activate autoreactive F1 B cells to produce autoantibodies. This state of "split tolerance" is closely associated with the development of a lupus-like autoimmune syndrome. The LFA-1 integrin plays a relevant role in homing, intercellular adhesion and tranduction of co-stimulatory signals in leukocytes. Because of the beneficial effects of anti-LFA-1 monoclonal antibodies (mAb) treatment in various models of organ transplantation and autoimmune disease, we have investigated if such a treatment could interfere with the induction of neonatal tolerance or the development of the autoimmune syndrome in F1 cell-injected newborn mice. For this purpose, BALB/c mice neonatally injected with F1 cells were treated from day 1 up to day 15 with a non-cytotoxic anti-LFA-1 (CD11a) mAb. Anti-LFA-1 mAb treatment interfered with the persistence of a stable chimerism and with the establishment of CTL tolerance, as shown by rejection of allogeneic skin grafts and F1 B cells, and by a normal in vitro CTL activity against the corresponding alloantigens. As a consequence, these mice did not develop the characteristic autoimmune features seen in close association with an effective induction of CTL tolerance to alloantigens. These results stress the importance of the interactions between LFA-1 and its ligands during the neonatal induction of tolerance to alloantigens.
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PMID:Anti-LFA-1 (CD11a) monoclonal antibody interferes with neonatal induction of tolerance to alloantigens. 790 37

Though vasculitic diseases have been claimed to be associated with anti-endothelial cells antibodies (AECA), there is a widespread awareness of the limitations of the tests currently in use. Our objective was therefore to establish clones, in the hope that some of them would express disease-specific membrane autoantigens. Two EC lines and 7 clones were established by fusing human umbilical vein EC with epithelial A549/8 cells, and cloning by limiting dilution. An additional clone was derived from the EA.hy 926 cell line. All clones carried EC markers, such as thrombomoduline (TM) and platelet-EC adhesion molecule 1 but differed from each other, depending on whether they expressed HLA class II antigen, LFA-1, thrombospondin receptor or von Willebrand factor (vWf) antigen. Clones were also characterized by their ability to release tissue plasminogen activator, interleukin 6, TM and vWf. This panel is meant to distinguish reactivities of AECA.
Lupus 1996 Apr
PMID:Establishment and characterization of permanent human endothelial cell clones. 874 22

IFN gamma is a costimulator of macrophage activation and it plays an important role as a proinflammatory cytokine by upregulation of adhesion molecules and MHC antigens. In this study we tested the role of IFN gamma in a model of endotoxin-induced glomerulonephritis. A systemic lupus-like disease was induced by injection of 50 micrograms bacterial LPS twice a week for 4 weeks in wild-type and in IFN gamma receptor-deficient (IFN gamma R-/-) mice. The renal cortex was examined by immunofluorescence and by light microscopy. LPS treatment induced an increase in serum levels of IgG and anti-dsDNA antibodies. A mild glomerulonephritis was characterized morphologically, but proteinuria was not observed. The main histological features of glomerulonephritis were an increase in ICAM-1 expression, deposition of immune complexes and of complement in the glomeruli, increased mesangial matrix and mesangial hypercellularity. The number of intraglomerular leukocytes, detected by MHC class-II and LFA-1 expression increased roughly 4-fold. All those alterations took place in a similar manner in wild-type and in IFN gamma R-/-mice. Therefore it is concluded that IFN gamma does not play an important role in the development of endotoxic glomerulonephritis.
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PMID:Lipopolysaccharide-induced glomerulonephritis develops in the absence of interferon-gamma signaling. 886 25


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