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)

Estrogen is thought to contribute to the onset of systemic lupus erythematosus (SLE) in women through mechanisms that are not completely understood. Although estrogen serves as a negative regulator in normal hematopoietic development, little research has been conducted examining alteration in hematopoietic development triggered by estrogen in lupus-susceptible individuals. We examined whether estrogen and other factors could influence colony formation of bone marrow cells obtained from normal and lupus-susceptible mice. Bone marrow cells isolated from New Zealand Black (NZB) and lupus-prone New Zealand Black and New Zealand White cross (NZB/W) mice were cultured in the presence of granulocyte-macrophage colony stimulating factor (GM-CSF) alone or in combination with estrogen, thrombopoietin (TPO), tamoxifen, estrogen and TPO. or estrogen and tamoxifen, and plated in methylcellulose culture medium. Plates were scored for the number of CFU-GM (colony forming unit granulocyte-macrophage) colonies after 6d in culture. For females of both mouse strains, estrogen significantly decreased (P < 0.05) the number of GM colonies. Co-treatment of NZB/W cells, but not NZB cells, with TPO or tamoxifen reversed the suppressive action of estrogen (P < 0.05). In contrast, while estrogen did suppress colony formation from cells of NZB/W males (P < 0.05), neither TPO nor tamoxifen reversed this effect. Our results indicate that the sensitivity of bone marrow cells isolated from both female and male NZB/W lupus-prone mice to hormones/growth factors is qualitatively different from cells of NZB mice, and suggest that hematopoietic alterations at the level of the bone marrow may be related to the pathogenesis of SLE.
Lupus 2000
PMID:Altered bone marrow cell sensitivity in the lupus-prone NZB/W mouse: regulation of CFU-GM colony formation by estrogen, tamoxifen and thrombopoietin. 1086 98

Estrogen is believed to contribute to the development of the autoimmune disorder systemic lupus erythematosus (SLE) (lupus) in women. We hypothesized that estrogen might promote the development of lupus by altering apoptosis of bone marrow cells, perhaps through regulation of the apoptotic proteins Bax and Bcl-2. We compared the effects of estrogen (E2) and thrombopoietin (TPO) on the expression of Bax or Bcl-2 in bone marrow cells isolated from female non-lupus (NZW or NZB parental strains) or lupus-prone (NZB and NZW cross; NZB/W) mice. We report that the basal level of Bax in parental bone marrow cells was significantly greater than that of cells from NZB/W animals. Treatment of NZB or NZW marrow cells with E2 resulted in a significant decrease in Bax expression, which was completely reversed upon co-treatment with TPO. Bax expression was not significantly altered by E2 and/or TPO in NZB/W cells. Bcl-2 levels did not differ between murine strains under basal or hormone-treated conditions. Lower basal expression of Bax protein was associated with significantly less apoptosis for NZB/W marrow cells. In addition, there were significantly greater numbers of cells in bone marrow of lupus-susceptible animals. Our results indicate that bone marrow cells of NZB/W animals differ physiologically from those of NZW or NZB mice, and suggest that decreased expression of Bax in bone marrow precursors may lead to decreased apoptosis of mature blood cells in lupus-susceptible mice.
Lupus 2001
PMID:Altered Bax expression and decreased apoptosis in bone marrow cells of lupus-susceptible NZB/W mice. 1178 88

Thrombocytopenia is a common phenomenon in patients suffering from systemic lupus erythematosus (SLE). The cause of thrombocytopenia in SLE, however, is poorly understood. In this study, 100 patients with SLE were evaluated for serum thrombopoietin levels, anti-thrombopoietin antibodies and routine laboratory parameters such as peripheral blood counts, parameters of blood chemistry and immunologic parameters of SLE. The median platelet count of SLE patients was 230 g/l and 19 were thrombocytopenic (range 8-148 g/l). Thrombopoietin levels in SLE patients were found to be significantly higher than in healthy controls (n = 96; median, 117 pg/ml vs 64 pg/ml, P < 0.01). When excluding thrombocytopenic SLE patients, thrombopoietin levels in SLE were still above controls (111 pg/ml, P < 0.01). The thrombopoietin levels were correlated to erythrocyte sedimentation rate and ECLAM score of disease activity, and inversely correlated to complement factor C4, but not to the platelet count. Anti-thrombopoietin antibody reactivity was found in 23% of SLE patients. Interestingly, these patients had lower platelet counts than SLE patients without anti-thrombopoietin antibodies (median 174 g/l and 253 g/l, respectively, P < 0.01), but thrombopoietin levels were not significantly different. Taken together, thrombopoietin levels are significantly higher in the sera of SLE patients than in healthy controls and anti-thrombopoietin antibodies are frequently found.
Lupus 2002
PMID:Serum thrombopoietin levels and anti-thrombopoietin antibodies in systemic lupus erythematosus. 1204 85