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Abnormal cytokine production by bone marrow stromal cells of multiple myeloma patients in response to RPMI8226 myeloma cells

100%
Zdzisinska B., Bojarska-Junak A., Dmoszynska A., Kandefer-Szerszen M.
Archivum Immunologiae et Therapiae Experimentalis
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2008
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vol. 56
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issue 3
207-221
EN
Introduction Recent studies indicate that bone marrow stromal cells (BMSCs) derived from patients with multiple myeloma (MM) differ from those of healthy donors in their expression of extracellular matrix compounds and in cytokine production. It is not known whether these abnormalities are primary or are acquired by BMSCs on contact with MM cells. Materials and Methods: Interleukin (IL)-6, IL-11, IL-10, and tumor necrosis factor (TNF)-alpha production by CD166+ mesenchymal BMSCs and the CD38+/CD138+ RPMI8226 myeloma cell line cultivated in vitro in monocultures or co-cultivated under cell-to-cell contact or non-contact conditions in the presence of a tissue culture insert were measured. Intracellular cytokines were measured by flow cytometry analysis as the percentage of cytokine-producing cells or by mean fluorescence intensity as the level of cytokine expression in cells. Additionally, ELISA was used to measure IL-6, soluble IL-6 receptor (sIL-6R), IL-11, IL-10, TNF- alpha, B-cell-activating factor of the TNF family (BAFF), hepatocyte growth factor (HGF), and osteopontin (OPN) production in the supernatants of the cultures and co-cultures. Results A higher ability of the BMSCs of MM patients than in controls was detected to produce IL-6, IL-10, TNF- alpha, OPN, and especially HGF and BAFF in response to the RPMI8226 cells. Moreover, the BMSCs of the MM patients significantly enhanced the production of sIL-6R by the RPMI8226 cells. Discussion Cytokines over-expressed by BMSCs of MM patients can function as growth factors for myeloma cells (IL-6, IL-10, HGF), migration stimulatory factors for tumor plasma cells (TNF-alpha, HGF), adhesion stimulatory factors (HGF, BAFF and OPN), stimulators of osteoclastogenesis (IL-6, TNF-alpha), and angiogenic factors (TNF-alpha). The results of this experiment strongly suggest that the BMSCs from MM patients differed in spontaneous and myeloma cell-induced production of cytokines, especially of HGF and BAFF, and these abnormalities were both primary and acquired by the BMSCs on contact with the MM cells. This in turn suggests the presence of an undefined, autocrine stimulation pathway resulting in a prolonged production of cytokines even in long-term cultures in vitro and in vivo. These abnormalities might provide optimal conditions for the proliferation and differentiation of residual tumor cells or their precursors in the affected bone marrow.
2

Common molecule CD43.

100%
Rupniewska Z., Rolinski J., Bojarska-Junak A.
Postępy Higieny i Medycyny Doświadczalnej
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2000
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vol. 54
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issue 5
619-638
EN
CD43 is an integral cell membrane mucin appearing on hematopoietic cells in embryonic life probably on cells of vitellus bag, in embryonic and foetal liver and in foetal bone marrow. In adults CD43 occurs both on bone marrow hematopoietic sten cells as well as on peripheral mature white blood leukocytes with the exception of resting B lymphocytes. CD43 is also found on tissue macrophage, dendritic cells, smooth muscle cells, epithelium and endothelium. CD43 expression was detected on cells of leukaemias myeloid and lymphoid, lymphoma cells and metastases of solid neoplasms. Due to the elongated, twig-resembling shapes and numerous negatively charged rests of sialic acid CD43 can act in an anti-adhesive fashion e.g. disturbing ICAM-1 (CD54) ? LFA-1 (CD11A/CD18) interaction. Alternatively, in certain conditions CD43 can be pro-adhesive. So, e.g. adhesion hematopoietic progenitor cells to stromal bone marrow cells partly depends on CD34-CD43 cooperation. Similarly, according to the degree of cell maturity and the kind of cell line, CD43 can induce either activation or cell apoptosis. So, binding CD43 by specific monoclonal antibody induces activation and proliferation of T cells and also the oxidation burst of monocytes and neutrophils. On the other hand, CD43 induces apoptosis, especially in dividing progenitor hematopoietic stem cells.
3
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Diurnal and seasonal changes in endogenous melatonin levels in the blood plasma in dogs

88%
Kowalski C. J., Madany J., Zań R. S., Roliński Z., Bojarska-Junak A.
Polish Journal of Veterinary Sciences
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2013
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issue 4
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