Effect of synthetic retinoid, TAC-101, on experimental autoimmune disease.
The effect of 4-[3,5-bis(trimethylsilyl)benzamido] benzoic acid (TAC-101), one of the synthetic retinoids, on collagen-induced arthritis (CIA) in mice and experimental autoimmune encephalomyelitis (EAE) in rats was studied. TAC-101 at doses of 5 and 20 mg/kg clearly inhibited the development of CIA in terms of the swelling of fore- and hind-limbs and bone destruction in knee joints. TAC-101 also suppressed the production of anti-type II collagen (CII) IgG antibody and delayed-type hypersensitivity (DTH) against CII. In addition, TAC-101 delayed the onset and development of EAE but did not affect the maximum symptom of EAE in rats. The elevation of serum antimyelin basic protein (MBP) antibody and DTH to MBP on day 13 clearly suppressed by TAC-101 in EAE rats. Moreover, TAC-101 inhibited the IL-1beta-induced PGE(2) production by MG-63 cells, human osteoblast-like cells, through the suppression of cyclooxygenase II mRNA expression. These findings suggest that TAC-101 inhibits CIA in mice and EAE in rats due to the suppression of immune response to auto-antigen and the production of PGE(2).
Miyagawa
Naoki
N
Department of Pharmacology, Gifu Pharmaceutical University, Gifu, Japan.
Homma
Takeyasu
T
Kagechika
Hiroyuki
H
Shudo
Koichi
K
Nagai
Hiroichi
H
D000818:Animals; D001169:Arthritis, Experimental / Q000188:drug therapy / Q000276:immunology*; D001324:Autoantigens / Q000276:immunology; D001565:Benzoates / Q000627:therapeutic use*; D002460:Cell Line; D051546:Cyclooxygenase 2; D016207:Cytokines / Q000096:biosynthesis / Q000276:immunology; D015232:Dinoprostone / Q000096:biosynthesis / Q000276:immunology; D004681:Encephalomyelitis, Autoimmune, Experimental / Q000188:drug therapy / Q000276:immunology*; D005260:Female; D006801:Humans; D006968:Hypersensitivity, Delayed / Q000276:immunology / Q000517:prevention & control*; D007166:Immunosuppressive Agents / Q000627:therapeutic use*; D007527:Isoenzymes / Q000096:biosynthesis; D007719:Knee Joint / Q000187:drug effects / Q000473:pathology; D008297:Male; D008565:Membrane Proteins; D051379:Mice; D008815:Mice, Inbred Strains; D004676:Myelin Basic Protein / Q000276:immunology; D010006:Osteoblasts / Q000201:enzymology; D011239:Prednisolone / Q000031:analogs & derivatives* / Q000627:therapeutic use; D011451:Prostaglandin-Endoperoxide Synthases / Q000096:biosynthesis; D051381:Rats; D011919:Rats, Inbred Strains; D012176:Retinoids / Q000627:therapeutic use*; D014297:Trimethylsilyl Compounds / Q000627:therapeutic use*
D001324:Autoantigens; D001565:Benzoates; D016207:Cytokines; D007166:Immunosuppressive Agents; D007527:Isoenzymes; D008565:Membrane Proteins; D004676:Myelin Basic Protein; D012176:Retinoids; C112689:TAC 101; D014297:Trimethylsilyl Compounds; C009935:prednisolone acetate; D011239:Prednisolone; D051546:Cyclooxygenase 2; C496540:PTGS2 protein, human; D011451:Prostaglandin-Endoperoxide Synthases; D015232:Dinoprostone