Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0155339 (Brown)
 12,436 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Heparin blocks the phorbol ester-induced progression of nontransformed cells through the G0/G1 phase (Wright, T.C., L.A. Pukac, J.J. Castellot, M.J. Karnovsky, R.A. Levine, H.-Y. Kim-Park, and J. Campisi. 1989. Proc. Natl. Acad. Sci. USA. 86: 3199-3203) or G1 to S phase (Reilly, C. F., M. S. Kindy, K. E. Brown, R. D. Rosenberg, and G. E Sonenshein. 1989. J. Biol. Chem. 264:6990-6995) of the cell cycle. Cell cycle arrest was associated with decreased levels of stage-specific mRNAs suggesting transcriptional regulation of cell growth. In the present report, we show that heparin selectively repressed TPA-inducible AP-1-mediated gene expression. Heparin-induced trans-repression was observed in primary vascular smooth muscle cells, as well as in the transformed HeLa cell line and in nondifferentiated F9 teratocarcinoma cells. Inhibition of AP-1-mediated trans-activation occurred with heparin and pentosan polysulfate but not with chondroitin sulfate A or C. Heparin-binding peptides or heparitinase I addition to nuclear lysates of heparin-treated cells allowed enhanced recovery of endogenous AP-1-specific DNA binding activity. We propose a model in which nuclear glycosaminoglycans play a trans-regulatory role in altering the patterns of inducible gene expression.
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PMID:Trans-repressor activity of nuclear glycosaminoglycans on Fos and Jun/AP-1 oncoprotein-mediated transcription. 173 Jul 47

Most Hodgkin's mononuclear cells and Reed-Sternberg (H-RS) cells are characterized by the expression of the antigen CD30, but not of T or B cell markers. A few H-RS cells, however, may express a limited number of T or B cell markers. Whether this expression is sufficient to allow the conclusion that H-RS cells are derived from T and/or B cells has been debated vigorously. The present study examined whether CD30 and aberrant T and B cell markers are expressed in cell lines that are well documented as being derived from the granulocyte/monocyte/histiocyte lineage. These cells included HL-60, KG-1, ML-1, THP-1, and U-937. Four other cell lines derived from patients with leukemias/lymphomas of monocytic or granulocytic origins also were studied. These cells included BV173, CML-Brown, CTV-2, and SU-DHL-1. If aberrant expression is detected, by analogy one may expect that rare T or B cell marker expression may occur in H-RS cells, because abundant evidence has indicated that H-RS cells may be related to cells in histiocyte lineage. In all nine of the cell lines studied, it was confirmed that numerous monocyte/granulocyte markers were expressed. The marker expression was enhanced after cells were induced to differentiate with phorbol ester (TPA) and tumor necrosis factor (TNF). It was noted that several T and B cell markers also were expressed by these cells. Unlike the expression of monocyte/granulocyte markers, the expression of T or B cell markers was not affected, or only minimally affected, by treatment of the cells with TPA or TNF. Five of the cell lines (BV173, CML-Brown, CTV-2, SU-DHL-1, and THP-1) were shown to be CD30-positive. In CTV-2 and BV173, the expression of CD30 was greatly increased after induction with phorbol ester or TNF. Based on these studies, the following conclusions were reached: 1) The expression of aberrant B or T cell markers is not an uncommon finding in granulocyte/monocyte/histiocyte-related neoplastic cells. 2) The expression of granulocyte/monocyte markers in these cells is related to the state of cell differentiation, whereas the expression of T or B cell markers is not. 3) CD30 is not necessarily a proliferation-related antigen, and its expression is not a sole property of T or B cells, but can be present in granulocyte/monocyte/histiocyte-related cells.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:Aberrant expression of T cell and B cell markers in myelocyte/monocyte/histiocyte-derived lymphoma and leukemia cells. Is the infrequent expression of T/B cell markers sufficient to establish a lymphoid origin for Hodgkin's Reed-Sternberg cells? 249 2

1. IL-13 is an important mediator in inflammatory diseases such as asthma. IL-13 is mainly produced by T cells. However, signalling pathways leading to induction of this cytokine are not well-characterized. We analysed the regulation of IL-13 in human peripheral blood mononuclear cells and CD4(+) T cells. 2. Cyclosporine (CsA) and FK-506 inhibited IL-13 synthesis, when cells were stimulated by TPA/ionomycin. However, stimulation by alpha-CD3/alpha-CD28 led to an enhanced IL-13 synthesis. 3. NF-kappa B inhibitor N-tosyl-L-lysine chloromethylketone (TLCK) inhibited IL-13 synthesis more effectively after TPA/ionomycin stimulation. After alpha-CD3/alpha-CD28 stimulation, only 300 microM TLCK inhibited IL-13 synthesis. Dexamethasone inhibited IL-13 equally effective after alpha-CD3/alpha-CD28 and TPA/ionomycin stimulation. 4. p38 MAPK inhibitor SB203580 inhibited IL-13 synthesis only partially. MEK inhibitor U0126 inhibited TPA/ionomycin induced IL-13 synthesis very effectively, whereas alpha-CD3/alpha-CD28 stimulated IL-13 induction was resistant to this drug. 5. These results were confirmed in purified CD4(+) T cells. In difference to PBMCs alpha-CD3/alpha-CD28 stimulated IL-13 synthesis was effectively inhibited by CsA, FK-506 and U0126. 6. Therefore U0126 was tested in an animal model of allergic asthma. We could demonstrate for the first time that inhibition of the MEK - ERK cascade is a therapeutic option for asthma. Intraperitoneal administration of 10 mg kg(-1) U0126 reduced lung eosinophilia in ovalbumin-challenged Brown Norway rats by 44%. 7. These results demonstrate that different signalling pathways are involved in regulating IL-13 synthesis in primary human T cells. Characterizing highly potent inhibitors of IL-13 synthesis can be exploited to identify new drugs to treat immunological diseases such as asthma.
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PMID:Regulation of IL-13 synthesis in human lymphocytes: implications for asthma therapy. 1195 94