LL-Z1271alpha: an interleukin-1beta production inhibitor.
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.
Ichikawa
K
K
Exploratory Medicinal Sciences, PGRD, Nagoya Laboratories, Pfizer Pharmaceuticals Inc., 5-Gochi Taketoyo-cho, Chita-gun, Aichi 470-2393, Japan. katsuomi ichikawa@japan.pfizer.com
Inagaki
T
T
Kachi-Tonai
H
H
Kojima
Y
Y
Nakamura
T
T
Nishida
H
H
Ueno
Y
Y
Binding
P
P
Gabel
C A
CA
Lucas
V
V
McNiff
P A
PA
Kojima
N
N
D000255:Adenosine Triphosphate / Q000494:pharmacology; D000818:Animals; D061945:Caspase Inhibitors; D002478:Cells, Cultured; D004305:Dose-Response Relationship, Drug; D006801:Humans; D007375:Interleukin-1 / Q000096:biosynthesis*; D008070:Lipopolysaccharides / Q000494:pharmacology; D051379:Mice; D013729:Terpenes / Q000494:pharmacology*
D061945:Caspase Inhibitors; D007375:Interleukin-1; D008070:Lipopolysaccharides; D013729:Terpenes; C013363:LL-Z 1271alpha; D000255:Adenosine Triphosphate