Biomaterial Database

Modulation of interleukin-1 activity on murine thymocytes by various inhibitors of arachidonic acid oxygenation. 1988

R M Schultz, and M G Altom

Department of Immunology Research, Lilly Research Laboratories, Lilly Corporate Center, Indianapolis, IN 46285.

A variety of cyclooxygenase (FCO) and 5-lipoxygenase (5-LPO) inhibitors were tested for their ability to modulate murine thymocyte proliferation induced by IL-1 and suboptimal levels of the mitogen phytohemagglutinin (PHA). The contribution of drug toxicity to inhibition of 3H-thymidine incorporation was estimated by measuring MTT (3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide) formazan production in the thymocyte cultures at the end of the assay. Cyclosporin A and dexamethasone, two positive control compounds, potently inhibited thymocyte proliferation at extremely low concentrations (0.01 and 0.001 micrograms/ml respectively), although activity roughly paralleled toxicity. In contrast, 5-LPO inhibitors (AA-861, BW-755c, and ETYA), but not selective FCO inhibitors (ibuprofen and indomethacin), suppressed lymphoproliferation at nontoxic concentrations, suggesting that products of the 5-LPO pathway may mediate the thymocyte proliferative response induced by IL-1/PHA. Attempts to counteract the suppressive activity of 5-LPO inhibitors by addition of leukotriene (LT) B4, LTC4, LTE4, 5-HETE, and 15-HETE were unsuccessful.

UI	MeSH Term	Description	Entries
D007375	Interleukin-1	A soluble factor produced by MONOCYTES; MACROPHAGES, and other cells which activates T-lymphocytes and potentiates their response to mitogens or antigens. Interleukin-1 is a general term refers to either of the two distinct proteins, INTERLEUKIN-1ALPHA and INTERLEUKIN-1BETA. The biological effects of IL-1 include the ability to replace macrophage requirements for T-cell activation.	IL-1,Lymphocyte-Activating Factor,Epidermal Cell Derived Thymocyte-Activating Factor,Interleukin I,Macrophage Cell Factor,T Helper Factor,Epidermal Cell Derived Thymocyte Activating Factor,Interleukin 1,Lymphocyte Activating Factor
D008084	Lipoxygenase	An enzyme of the oxidoreductase class primarily found in PLANTS. It catalyzes reactions between linoleate and other fatty acids and oxygen to form hydroperoxy-fatty acid derivatives.	Lipoxidase,Linoleate-Oxygen Oxidoreductase,Lipoxygenase-1,Lipoxygenase-2,Linoleate Oxygen Oxidoreductase,Lipoxygenase 1,Lipoxygenase 2,Oxidoreductase, Linoleate-Oxygen
D008213	Lymphocyte Activation	Morphologic alteration of small B LYMPHOCYTES or T LYMPHOCYTES in culture into large blast-like cells able to synthesize DNA and RNA and to divide mitotically. It is induced by INTERLEUKINS; MITOGENS such as PHYTOHEMAGGLUTININS, and by specific ANTIGENS. It may also occur in vivo as in GRAFT REJECTION.	Blast Transformation,Blastogenesis,Lymphoblast Transformation,Lymphocyte Stimulation,Lymphocyte Transformation,Transformation, Blast,Transformation, Lymphoblast,Transformation, Lymphocyte,Activation, Lymphocyte,Stimulation, Lymphocyte
D008297	Male		Males
D008815	Mice, Inbred Strains	Genetically identical individuals developed from brother and sister matings which have been carried out for twenty or more generations, or by parent x offspring matings carried out with certain restrictions. All animals within an inbred strain trace back to a common ancestor in the twentieth generation.	Inbred Mouse Strains,Inbred Strain of Mice,Inbred Strain of Mouse,Inbred Strains of Mice,Mouse, Inbred Strain,Inbred Mouse Strain,Mouse Inbred Strain,Mouse Inbred Strains,Mouse Strain, Inbred,Mouse Strains, Inbred,Strain, Inbred Mouse,Strains, Inbred Mouse
D003524	Cyclosporins	A group of closely related cyclic undecapeptides from the fungi Trichoderma polysporum and Cylindocarpon lucidum. They have some antineoplastic and antifungal action and significant immunosuppressive effects. Cyclosporins have been proposed as adjuvants in tissue and organ transplantation to suppress graft rejection.	Cyclosporines
D003907	Dexamethasone	An anti-inflammatory 9-fluoro-glucocorticoid.	Hexadecadrol,Decaject,Decaject-L.A.,Decameth,Decaspray,Dexasone,Dexpak,Hexadrol,Maxidex,Methylfluorprednisolone,Millicorten,Oradexon,Decaject L.A.
D000818	Animals	Unicellular or multicellular, heterotrophic organisms, that have sensation and the power of voluntary movement. Under the older five kingdom paradigm, Animalia was one of the kingdoms. Under the modern three domain model, Animalia represents one of the many groups in the domain EUKARYOTA.	Animal,Metazoa,Animalia
D001094	Arachidonate 5-Lipoxygenase	An enzyme that catalyzes the oxidation of arachidonic acid to yield 5-hydroperoxyarachidonate (5-HPETE) which is rapidly converted by a peroxidase to 5-hydroxy-6,8,11,14-eicosatetraenoate (5-HETE). The 5-hydroperoxides are preferentially formed in leukocytes.	5-Lipoxygenase,Arachidonic Acid 5-Lipoxygenase,LTA4 Synthase,Leukotriene A Synthase,Leukotriene A4 Synthase,Leukotriene A4 Synthetase,5 Lipoxygenase,5-Lipoxygenase, Arachidonate,5-Lipoxygenase, Arachidonic Acid,Arachidonate 5 Lipoxygenase,Arachidonic Acid 5 Lipoxygenase,Synthase, LTA4,Synthase, Leukotriene A,Synthase, Leukotriene A4,Synthetase, Leukotriene A4
D001095	Arachidonic Acids		Eicosatetraenoic Acids,Acids, Arachidonic,Acids, Eicosatetraenoic