摘要:

AbstractThe present paper examines the effect of basic fibroblast growth factor (bFGF) on the proliferation of teratoma-derived cell lines having increased tumorigenic properties isolated from the non-tumorigenic adipogenic cell line 1246. Although FGF is a mitogen for the non tumorigenic 1246 cells and for the moderately tumorigenic 1246-3A cells derived from the 1246 cells, bFGF inhibits the proliferation and DNA synthesis of the highly tumorigenic PC cells starting at concentration as low as 30 pg/ml. The inhibitory effect of FGF on PC cell growth is irreversible as demonstrated by the inability of the cells to resume proliferation once FGF is removed from the culture medium. Comparison ofl25I-bFGF binding to the three cell lines was performed. Based on the Scatchard analysis of the binding data, PC cells display only low affinity class of FGF binding sites whereas 1246 and 1246-3A cells presented also high affinity binding sites. The inhibitory effect of FGF on PC cells did not go through activation of a PKC mediated pathway, which is also known to inhibit PC cell proliferation, since FGF inhibition of PC cell growth was still apparent after PKC down regulation. FGF was still able to transiently stimulate the expression of mRNA for early growth associated genes as demonstrated byc-mycandc-fosexpression, although it inhibited cell proliferation on PC cells. Our data demonstrate that the highly tumorigenic teratoma cells acquire an inhibitory response for a factor which is growth stimulatory to non-tumorigenic and moderately tumorigenic cells from which they are derived.

ISSN:0897-7194    

DOI:10.3109/08977199309010827

出版商:Taylor&Francis    

年代:1993

数据来源: Taylor

摘要:

AbstractThe present study attempts to define the difficulties in evaluating the properties of the hemoregulatory peptide AcSDKP usingin vitroassays. In fact, in the presence of sera, which are generally added to basic culture media, AcSDKP is catabolized by proteases present in the serum. The kinetics of AcSDKP degradation depends on the nature and on the concentration of the added serum. Inin vitroconditions, the half life of this peptide can be increased by the addition of 1 M captopril, a metalloprotease inhibitor. Thus, these points need to be considered in designing experiments to study the effects of AcSDKP.

ISSN:0897-7194    

DOI:10.3109/08977199309010828

出版商:Taylor&Francis    

年代:1993

数据来源: Taylor

摘要:

AbstractIn an attempt to elucidate the intricate structure and possibly the signal transduction pathway of the interleukin-2 receptor (IL-2R) we tried to produce monoclonal antibodies against putative human IL-2R-associated molecules which precipitated from YT2C2 cells with a monoclonal antibody (Mikβ3) against the human IL-2Rβchain. One of the antibodies obtained (7xA10) recognizes a cell surface molecule of about 120 kDa (p120). Cross-linking of [125I]-IL-2 and immunoprecipitation with 7xA10 suggest that the p120 protein may somehow associate physically with the IL-2Rβchain. Although p120 itself did not bind IL-2, and 7xA10 did not inhibit IL-2 binding to the IL-2R, growth of the human IL-2-dependent cell lines ED40515 and Kit225 was completely inhibited by adding 7xA10 to the culture at a relatively low concentration (0.2g/ml). At a higher concentration (2g/ml) 7xA10 inhibited the growth of YTC3 and YT2C2 cells expressing IL-2Rs with high and intermediate affinities, respectively. The B cell line FLEB-14 and the erythroid cell line K562, which both express p120 as determined by flow cytometry, but no IL-2Rαorβchains showed only slight proliferation changes at high 7xA10 concentrations. Out of 16 lymphocyte cell lines tested so far, only Molt-4, Raji and Daudi did not express p120, and therefore 7xA10 did not influence their growth behavior. p120 might be a new IL-2R association molecule which seems to play a certain role in the growth regulation of various lymphoid cell lines.

ISSN:0897-7194    

DOI:10.3109/08977199309010829

出版商:Taylor&Francis    

年代:1993

数据来源: Taylor

摘要:

AbstractWe have recently reported that nerve growth factor (NGF) increases in the synovium of patients affected by rheumatoid arthritis and in the synovium of pharmacologically-induced arthritis in animal models. In the present study, we demonstrate that arthritic transgenic mice which carry and express the human TNF gene (Tg197) also express elevated levels of NGF, and that subcutaneous injection of NGF-antibodies attenuates the loss of body weight caused by the developement of disease in these mice. Along with our previous findings, which show an increase in the level of NGF during the acute phase of other autoimmune diseases, these results suggest a role of NGF in these pathologies. The functional significance of NGF in rheumatoid arthritis (RA) is currently under study.

ISSN:0897-7194    

DOI:10.3109/08977199309010830

出版商:Taylor&Francis    

年代:1993

数据来源: Taylor

摘要:

AbstractObjective. To study the regulation of macrophage-colony stimulating factor (M-CSF) formationin vitroby human synovial fibroblast-like cells.Methods. Human synovial cell explant cultures were established using cells from non-rheumatoid donors. M-CSF antigen was measured by immunoassay, and messenger RNA (mRNA) levels were determined by Northern blot.Results. The cytokines, interleukin-1 (IL-1), tumor necrosis factora (TNFα), interferon-γ(IFN-γ) and IL-4, increased production of M-CSF above constitutive levels. The presence of the cyclooxygenase inhibitor, indomethacin, potentiated the action of IL-1 on M-CSF synthesis, suggesting that an endogenous cydooxygenase product(s) can down-regulate M-CSF formation. Changes in M-CSF mRNA levels paralleled those in protein levels. The glucocorticoid, dexamethasone, and the retinoid, all-trans retinoic acid, stimulated M-CSF formation. The control of M-CSF synthesis in the synovial fibroblasts differs from that for granulocyte macrophage-CSF (GM-CSF) and granulocyte-CSF (G-CSF).Conclusion. These results suggest that cytokine-stimulated synovial fibroblasts may be a source of M-CSF production in the joints of patients with inflammatory arthritis; as a result, monocyte/macrophages may be activated, leading to perpetuation of the inflammation and destructive events occurring in these lesions.

ISSN:0897-7194    

DOI:10.3109/08977199309010831

出版商:Taylor&Francis    

年代:1993

数据来源: Taylor