Inhibition of IL-1-induced IL-6 production by synthetic retinoids.
The effects of retinoids and retinoid antagonists on IL-6 production in MC3T3-E1 cells were investigated. None of the synthetic retinoids examined stimulated IL-6 production, but all of them strongly inhibited IL-6 production induced by mouse IL-1 alpha. Their inhibitory activities correlated well with their differentiation-inducing activities in HL-60 assay or their binding affinities to nuclear retinoic acid receptors (RARs). Among three retinoid antagonists, two weak antagonists exhibited similar inhibition of mouse IL-1 alpha-induced IL-6 production, whereas a potent retinoid antagonist, 4-(13H-10,11,12,13-tetrahydro-10,10,13,13,15-pentamethyl-dinaph tho[2,3-b] [1,2-e]diazepin-7-yl)benzoic acid (LE540, 14), enhanced IL-6 production under the same conditions.
Kagechika
H
H
Faculty of Pharmaceutical Sciences, University of Tokyo, Japan.
Kawachi
E
E
Fukasawa
H
H
Saito
G
G
Iwanami
N
N
Umemiya
H
H
Hashimoto
Y
Y
Shudo
K
K
D016475:3T3 Cells; D000818:Animals; D003984:Dibenzazepines / Q000494:pharmacology; D007375:Interleukin-1 / Q000494:pharmacology*; D015850:Interleukin-6 / Q000096:biosynthesis*; D051379:Mice; D018168:Receptors, Retinoic Acid / Q000187:drug effects; D012176:Retinoids / Q000037:antagonists & inhibitors / Q000494:pharmacology*
D003984:Dibenzazepines; D007375:Interleukin-1; D015850:Interleukin-6; C104182:LE 135; C104183:LE 540; D018168:Receptors, Retinoic Acid; D012176:Retinoids