ABSTRACT
LL-Z1271alpha, a fungal metabolite, dose-dependently inhibited interleukin-1beta (IL-1beta) production in lipopolysaccharide (LPS)-stimulated human whole blood. Oral administration of LL-Z1271alpha to LPS-challenged mice caused significant lowering in the IL-1beta levels in peritoneal cavity. Data presented suggest that LL-Z1271alpha inhibits IL-1beta production by a novel mechanism as the inhibitory activity was not due to effects on caspase-1 (IL-1beta converting enzyme), the ATP-induced release mechanism or a lysosomotrophic effect.
Subject(s)
Interleukin-1/biosynthesis , Terpenes/pharmacology , Adenosine Triphosphate/pharmacology , Animals , Caspase Inhibitors , Cells, Cultured , Dose-Response Relationship, Drug , Humans , Lipopolysaccharides/pharmacology , MiceABSTRACT
Two new antibiotics, CJ-16,264 (I) and CJ-16,367 (II), were isolated from the fermentation broth of an unidentified fungus CL39457. These antibiotics have a pyrrolizidinone skeleton, first discovered in fungi. Compounds I and II inhibit the growth of Gram-positive multi-drug resistant bacteria and some Gram-negative strains such as Moraxella catarrhalis and Escherichia coli with altered permeability (imp). Comparison of an antibacterial profile between the two compounds suggested that the gamma-lactone portion of I is important for the activity.
