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)

In systemic Lupus erythematosus (SLE) spontaneous hyperreactivity of the cells of the immune system leads to the production of pathogenic autoantibodies. A hyperproliferative state of lymphocytes is indicated by the increased expression of nuclear oncogenes. We investigated the expression of a putative proto-oncogene, bcl-2, which is responsible for prolonged survival of lymphocytes and protection from programmed cell death. In 19 of 24 patients with SLE an increased concentration of bcl-2 mRNA was found in unstimulated circulating blood lymphocytes. The overexpression of the bcl-2 gene was more pronounced in patients with active SLE. A pathogenic role of increased bcl-2 expression and prolonged survival of autoimmune memory cells in SLE can be hypothesized.
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PMID:Transcriptional overexpression of the proto-oncogene bcl-2 in patients with systemic Lupus erythematosus. 152 45

The expression of c-myc proto-oncogene in spleen lymphocytes has been studied in lupus-prone mice (MRL/Mp-lpr/lpr), an animal model for the human autoimmune disease systemic lupus erythematosus, during the growing process, in comparison to control mice (MRL/Mp-+/+). By Northern blot assay and nuclear run on transcription assay, we demonstrated the enhancement of c-myc proto-oncogene expression in spleen lymphocytes from lupus-prone mice in comparison to control mice and the level of expression of c-myc proto-oncogene increased during the growing process and deterioration of lupus symptoms, such as production of autoantibodies and lymphoproliferation, in this study.
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PMID:Enhanced transcription of c-myc proto-oncogene in spleen lymphocytes from lupus-prone mice during the growing process. 268 25

Mice homozygous for the lpr gene spontaneously develop massive lymphoproliferation and an associated lupus-like autoimmune disease. In addition, the total lymphoid organs from these mice express high levels of mRNA for the c-myb proto-oncogene. Since enhanced c-myb mRNA is normally observed in immature thymic lymphocytes but not normal peripheral T cells, this may be indicative of the abnormal maturation state of lpr T lymphocytes. To determine whether the abnormal Lyt-2-, L3T4- (double negative) T lymphocytes in lpr mice express high c-myb, we purified this population by complement-mediated lysis with anti-L3T4 and Lyt-2 antibody from B6/lpr lymph nodes. We found that increased c-myb mRNA is expressed by this double-negative subset. To assess whether the high level of c-myb correlated with the aberrant undifferentiated state of these cells, we examined the effects of T cell differentiation inducers, phorbol ester and calcium ionophore, on c-myb expression. We found that c-myb levels were depressed after phorbol ester and calcium ionophore treatment. Concomitantly, transcriptional activation of the interleukin 2 receptor gene and progression of these cells through the cell cycle were observed. Thus, in B6/lpr double-negative T cells, the regulation of c-myb, interleukin 2 receptor, and cell proliferation may be interrelated. A combination of Northern hybridization and nuclear run-on transcription assays revealed two levels at which c-myb can be regulated in the double-negative T cell subset. The gene is transcriptionally regulated in untreated cells, but on induction with phorbol ester and calcium ionophore, the gene is negatively regulated via post-transcriptional mechanisms.
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PMID:The expression and regulation of c-myb transcription in B6/lpr Lyt-2-, L3T4-T lymphocytes. 311 95

The proliferative response of B lymphocytes to stimulation with anti-IgM antibodies and B-cell growth factors was studied in 27 patients with systemic lupus erythematosus (SLE) and 17 normal donors. In addition, the expression of messenger RNA of the proto-oncogene c-myc was also studied in B cells from SLE patients and normal donors. The proliferative response of lupus B cells to anti-IgM and B-cell growth factors as compared to normal B cells demonstrated a wide range of responses, 10 were lower than normal and 8 were either normal or supernormal. As compared to normals, expression of B-cell c-myc RNA from SLE patients was either normal or depressed. In general in patients with SLE there was a positive correlation between levels of c-myc expression and the degree of proliferation in B-cells after stimulation with anti-IgM and B-cell growth factors.
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PMID:Induction of c-myc expression early in the course of B-cell activation: studies in normal humans and patients with systemic lupus erythematosus. 348 78

Systemic autoimmune disease states are known to be associated with abnormal cell growth or differentiation. In the murine models of systemic lupus erythematosus (SLE), specific genotypes result in dysregulated growth of certain lymphocyte subpopulations. Although genes underlying autoimmune syndromes have been characterized by mendelian genetics, it has not yet been possible to characterize them at the molecular level. Recently, it has become clear that cellular proto-oncogenes can regulate cell growth and differentiation. Therefore, we have studied the expression of five different proto-oncogenes; myc, myb, abl, bas, and raf, in organs and cells of various autoimmune strains. These genes were selected because each has previously been associated with abnormal hemopoietic cell growth, and because each has been at least partially characterized at the molecular and functional level. We have found selective abnormal proto-oncogene expression associated with the characteristic abnormal cell growth or differentiation of lymphocytes of autoimmune mice. The lymph nodes of MRL-lpr/lpr mice are packed with unusual T cells. These had a marked increase in myb expression. There was a 20-40-fold increase in myb RNA in lymph nodes of lpr/lpr mice on several different genetic backgrounds. The gld/gld mouse has a very similar unusual T cell in the lymph nodes: it also had a comparable increase in myb RNA in the nodes. In contrast, myb expression was not elevated in the other autoimmune mouse strains lacking these abnormal T cells. Whereas such lpr/lpr mice had increased myb expression in the lymph nodes and splenic T cells, they had markedly subnormal myb expression in the thymus, an organ with high myb in normal and in the other autoimmune strains. These results suggest that one phase of intrathymic differentiation in other mice occurs in the periphery of lpr/lpr mice. The spleens of NZB and male BXSB mice had increased myc expression which was found to be associated with B cells upon cell separation. Similarly, increased bas and abl expression was associated with autoimmune B cells. The xid gene, which retards or prevents the expression of murine lupus by retarding B cell maturation, was associated in BXSB.xid, NZB.xid, and MRL-lpr/lpr.xid congenic mice with marked reduction in expression of myc, bas, and abl in the spleens containing B cells, but not of myb in the lpr/lpr.xid nodes containing primarily the unusual T cells. Raf expression was found to be associated in lpr/lpr and gld/gld mice with both the unusual T cells and splenic B cells.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:Oncogene expression in autoimmune mice. 391 23