Detection of interleukin-1 signal transduction inhibitors: action of protein kinase inhibitors.
The dysregulated production of IL-1 has been shown to play an important role in many pathological processes. Despite the apparent value of compounds able to inhibit either the secretion of IL-1 or its signal transduction pathway in a specific manner, there are no such compounds suitable for clinical use. A major problem in identifying novel and specific inhibitors of signal transduction is the lack of knowledge of the intracellular events which mediate the cellular actions of IL-1. In this study a simple cellular assay has been established to screen natural product and synthetic compound libraries for low molecular weight inhibitors of the cytokine signalling pathways of potential therapeutic value. In addition, we have studied the action of several known modulators of signal transduction on the actions of IL-1.
Brown
D
D
Xenova Ltd, Berkshire, U.K.
Sadeghi
R
R
Steel
J
J
Moore
M
M
Gammon
G
G
D002455:Cell Division / Q000187:drug effects; D004791:Enzyme Inhibitors / Q000494:pharmacology*; D004797:Enzyme-Linked Immunosorbent Assay; D006801:Humans; D007375:Interleukin-1 / Q000502:physiology*; D015850:Interleukin-6 / Q000096:biosynthesis; D007624:KB Cells; D007930:Leucine / Q000378:metabolism; D008970:Molecular Weight; D011493:Protein Kinase C / Q000037:antagonists & inhibitors; D047428:Protein Kinase Inhibitors; D020794:Receptor Protein-Tyrosine Kinases / Q000037:antagonists & inhibitors; D015398:Signal Transduction / Q000187:drug effects*; D013778:Tetrazolium Salts; D013844:Thiazoles
D004791:Enzyme Inhibitors; D007375:Interleukin-1; D015850:Interleukin-6; D047428:Protein Kinase Inhibitors; D013778:Tetrazolium Salts; D013844:Thiazoles; D020794:Receptor Protein-Tyrosine Kinases; D011493:Protein Kinase C; C022616:thiazolyl blue; D007930:Leucine