Down-regulation of human tumor necrosis factor-beta gene expression by cells with suppressive activity. 1996

D Aframian, and M Katzenellenbogen, and G Arad, and F Osman, and D Sayar, and M Ketzinel, and E Deutsch, and R Kaempfer
Department of Molecular Virology, The Hebrew University, Hadassah Medical School, Jerusalem, Israel.

Human TNF-beta (lymphotoxin) gene expression is down-regulated by immunosuppression. Induction of TNF-beta mRNA in lymphoid cells is greatly enhanced by gamma-irradiation, cyclophosphamide and cimetidine, agents that each inhibit activation of suppressive cells. The level of TNF-beta mRNA expressed in response to stimulation, whether by mitogen or antigen, is reduced strongly by concomitant activation of suppressive cell subsets. Removal of CD8 or CD11b cells leads to a pronounced superinduction of TNF-beta mRNA in the depleted cell population. Induction of TNF-beta mRNA precedes appearance of suppressive cell activity, allowing for temporary expression. The TNF-beta gene is as sensitive as IFN-gamma and IL-2 genes to suppression. Hence, three genes characteristically expressed in Th1 cells, encoding IL-2, IFN-gamma, and TNF-beta, are similarly regulated by cell-mediated suppression. Actual levels of TNF-beta during an immune response are determined by the balance between activities of expressing and suppressing cell subsets, both transiently manifested.

UI MeSH Term Description Entries
D007166 Immunosuppressive Agents Agents that suppress immune function by one of several mechanisms of action. Classical cytotoxic immunosuppressants act by inhibiting DNA synthesis. Others may act through activation of T-CELLS or by inhibiting the activation of HELPER CELLS. While immunosuppression has been brought about in the past primarily to prevent rejection of transplanted organs, new applications involving mediation of the effects of INTERLEUKINS and other CYTOKINES are emerging. Immunosuppressant,Immunosuppressive Agent,Immunosuppressants,Agent, Immunosuppressive,Agents, Immunosuppressive
D008233 Lymphotoxin-alpha A tumor necrosis factor family member that is released by activated LYMPHOCYTES. Soluble lymphotoxin is specific for TUMOR NECROSIS FACTOR RECEPTOR TYPE I; TUMOR NECROSIS FACTOR RECEPTOR TYPE II; and TUMOR NECROSIS FACTOR RECEPTOR SUPERFAMILY, MEMBER 14. Lymphotoxin-alpha can form a membrane-bound heterodimer with LYMPHOTOXIN-BETA that has specificity for the LYMPHOTOXIN BETA RECEPTOR. TNF Superfamily, Member 1,TNF-beta,Tumor Necrosis Factor Ligand Superfamily Member 1,Tumor Necrosis Factor-beta,Lymphotoxin,Lymphotoxin-alpha3,Soluble Lymphotoxin-alpha,alpha-Lymphotoxin,Lymphotoxin alpha,Lymphotoxin alpha3,Lymphotoxin-alpha, Soluble,Soluble Lymphotoxin alpha,Tumor Necrosis Factor beta,alpha Lymphotoxin
D002478 Cells, Cultured Cells propagated in vitro in special media conducive to their growth. Cultured cells are used to study developmental, morphologic, metabolic, physiologic, and genetic processes, among others. Cultured Cells,Cell, Cultured,Cultured Cell
D002927 Cimetidine A histamine congener, it competitively inhibits HISTAMINE binding to HISTAMINE H2 RECEPTORS. Cimetidine has a range of pharmacological actions. It inhibits GASTRIC ACID secretion, as well as PEPSIN and GASTRIN output. Altramet,Biomet,Biomet400,Cimetidine HCl,Cimetidine Hydrochloride,Eureceptor,Histodil,N-Cyano-N'-methyl-N''-(2-(((5-methyl-1H-imidazol-4-yl)methyl)thio)ethyl)guanidine,SK&F-92334,SKF-92334,Tagamet,HCl, Cimetidine,Hydrochloride, Cimetidine,SK&F 92334,SK&F92334,SKF 92334,SKF92334
D003520 Cyclophosphamide Precursor of an alkylating nitrogen mustard antineoplastic and immunosuppressive agent that must be activated in the LIVER to form the active aldophosphamide. It has been used in the treatment of LYMPHOMA and LEUKEMIA. Its side effect, ALOPECIA, has been used for defleecing sheep. Cyclophosphamide may also cause sterility, birth defects, mutations, and cancer. (+,-)-2-(bis(2-Chloroethyl)amino)tetrahydro-2H-1,3,2-oxazaphosphorine 2-Oxide Monohydrate,B-518,Cyclophosphamide Anhydrous,Cyclophosphamide Monohydrate,Cyclophosphamide, (R)-Isomer,Cyclophosphamide, (S)-Isomer,Cyclophosphane,Cytophosphan,Cytophosphane,Cytoxan,Endoxan,NSC-26271,Neosar,Procytox,Sendoxan,B 518,B518,NSC 26271,NSC26271
D005720 Gamma Rays Penetrating, high-energy electromagnetic radiation emitted from atomic nuclei during NUCLEAR DECAY. The range of wavelengths of emitted radiation is between 0.1 - 100 pm which overlaps the shorter, more energetic hard X-RAYS wavelengths. The distinction between gamma rays and X-rays is based on their radiation source. Gamma Wave,Gamma Radiation,Nuclear X-Rays,Radiation, Gamma,X-Rays, Nuclear,Gamma Radiations,Gamma Ray,Gamma Waves,Nuclear X Rays,Nuclear X-Ray,Ray, Gamma,Wave, Gamma,Waves, Gamma,X Rays, Nuclear,X-Ray, Nuclear
D005786 Gene Expression Regulation Any of the processes by which nuclear, cytoplasmic, or intercellular factors influence the differential control (induction or repression) of gene action at the level of transcription or translation. Gene Action Regulation,Regulation of Gene Expression,Expression Regulation, Gene,Regulation, Gene Action,Regulation, Gene Expression
D006801 Humans Members of the species Homo sapiens. Homo sapiens,Man (Taxonomy),Human,Man, Modern,Modern Man
D015536 Down-Regulation A negative regulatory effect on physiological processes at the molecular, cellular, or systemic level. At the molecular level, the major regulatory sites include membrane receptors, genes (GENE EXPRESSION REGULATION), mRNAs (RNA, MESSENGER), and proteins. Receptor Down-Regulation,Down-Regulation (Physiology),Downregulation,Down Regulation,Down-Regulation, Receptor
D016177 Macrophage-1 Antigen An adhesion-promoting leukocyte surface membrane heterodimer. The alpha subunit consists of the CD11b ANTIGEN and the beta subunit the CD18 ANTIGEN. The antigen, which is an integrin, functions both as a receptor for complement 3 and in cell-cell and cell-substrate adhesive interactions. CR3 Receptor,Complement 3 Receptor,Integrin alphaMbeta2,Mac-1 Antigen,Receptor, Complement 3,Adhesive Receptor Mac-1,Integrin alpha(M)beta(2),Integrin alpha-M beta-2,Mac-1 Adhesive Receptor,Mac-1 Receptor,Mo1 Antigen Receptor,Mo1 Glycoprotein Receptor,Receptor, CR3,Receptor, Mo1 Antigen,Receptor, Mo1 Glycoprotein,Adhesive Receptor, Mac-1,Antigen Receptor, Mo1,Antigen, Macrophage-1,Glycoprotein Receptor, Mo1,Integrin alpha M beta 2,Mac 1 Adhesive Receptor,Mac 1 Antigen,Mac 1 Receptor,Macrophage 1 Antigen,Receptor, Mac-1 Adhesive,alpha-M beta-2, Integrin,alphaMbeta2, Integrin

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