title: Aurothioglucose inhibits induced NF-kB and AP-1 activity by acting as an IL-1 functional antagonist.
abstract: We have designed a series of recombinant CAT genes to study IL-1 signal transduction in murine fibroblast NIH 3T3 cells. We demonstrate that the HSV thymidine kinase (tk) promoter does not respond to IL-1, but that IL-1 induction of this promoter is observed after insertion of either NF-kB or AP-1 binding sites upstream of the HSV tk cap-site. We have studied the effects of indomethacin, dexamethasone and aurothioglucose (which have been used in the treatment of patients affected by rheumatoid arthritis) in the IL-1 inducible CAT assay. We show that aurothioglucose or dexamethasone is able to inhibit IL-1 induced CAT activity whereas a non-steroidal anti-inflammatory drug (indomethacin) is inactive. Order of addition experiments indicate that aurothioglucose, which has disease-modifying activity in treated patients, acts as an IL-1 functional antagonist in this system.
authors.affiliation: Roche Products Ltd., Welwyn Garden City, UK.
authors.forename: D H
authors.initials: DH
authors.lastname: Williams
authors.forename: L J
authors.initials: LJ
authors.lastname: Jeffery
authors.forename: E J
authors.initials: EJ
authors.lastname: Murray
mesh_terms: D016475:3T3 Cells; D000818:Animals; D006051:Aurothioglucose / Q000494:pharmacology*; D001483:Base Sequence; D015500:Chloramphenicol O-Acetyltransferase / Q000235:genetics; D003907:Dexamethasone / Q000494:pharmacology; D007213:Indomethacin / Q000494:pharmacology; D007375:Interleukin-1 / Q000037:antagonists & inhibitors*; D051379:Mice; D008969:Molecular Sequence Data; D016328:NF-kappa B / Q000037:antagonists & inhibitors*; D009841:Oligonucleotides; D011401:Promoter Regions, Genetic; D016755:Proto-Oncogene Proteins c-jun / Q000037:antagonists & inhibitors*; D013937:Thymidine Kinase / Q000235:genetics
chemical_list: D007375:Interleukin-1; D016328:NF-kappa B; D009841:Oligonucleotides; D016755:Proto-Oncogene Proteins c-jun; D006051:Aurothioglucose; D003907:Dexamethasone; D015500:Chloramphenicol O-Acetyltransferase; D013937:Thymidine Kinase; D007213:Indomethacin