Effect of Am-80, a Synthetic Derivative of Retinoid, on Experimental Arthritis in Mice

Abstract

Am-80 is a newly snythesized retinoid with the structure of one aromatic amide among retinobenzoic acids. It exhibits specific biological activities of retinoic acid such as the activation of cellular differentiation and proliferation. We investigated the effect of Am-80 on collagen-induced arthritis (CIA) in mice and the immunopharmacological action on the production of several cytokines in the in vitro and in vivo models. Am-80, at doses of 0.3, 1 and 3 mg/kg, significantly inhibited the severity and development of the arthritis index, progression of foot pad swelling, bone damage and histopathological alterations. Am-80 also inhibited the production of anti-type II collagen (CII) IgG antibody, but did not affect the delayed-type hypersensitivity (DTH) response in arthritic mice. To determine the inhibitory mechanism of Am-80, we studied the effect of Am-80 on the production of cytokines. Am-80 did not affect the production of IFN-γ by Th1 cells (1E10.H2 cells) and IL-4 by Th2 cells (D10.G4.1 cells), respectively. Am-80 selectively inhibited bacterial lipopolysaccharide (LPS)-induced IL-6, but not TNF-α and IL-1β, production in mice. Moreover Am-80 inhibited IL-1β induced IL-6 production and IL-6 mRNA expression in human osteoblast-like cells (MG-63). The inhibition of IL-6 production by Am-80 was due to downregulation of the pretranscription or the transcription of IL-6 in MG 63 cells. These findings suggest that the inhibitory effect of Am-80 on CIA is partially by modulating the production of the proinflammatory cytokine, IL-6.

Effect of E6060 [4-{5-[7-Fluoro-4-(trifluoromethyl)benzo[b]furan-2-yl]-1H-2-pyrrolyl}benzoic Acid], a Novel Subtype-Selective Retinoid, on Lupus-Like Nephritis in Female (NZBxNZW)F1 Mice

“…It remarkably suppressed abnormal elevation of antibody production in those mice, and this effect seems to contribute, at least partly, to its antinephritic effect. Recently, an RAR-␣ selective synthetic retinoid, Am80, was reported to inhibit type II collagen-induced arthritis with a prominent reduction in anti-collagen IgG titer (Kuwabara et al, 1996;Nagai et al, 1999). Similarly, our RAR-␣-selective retinoid substantially inhibited not only anti-DNA antibody production (Fig.…”

“…Recently, Am80, a ligand with an affinity specific for RAR-␣, was reported to inhibit collagen-induced arthritis concomitantly with a prominent reduction in anti-collagen IgG titers (Kuwabara et al, 1996;Nagai et al, 1999). This report was the first to show that a retinoid could reduce Article, publication date, and citation information can be found at…”

The Effect of Am-80, a Synthetic Retinoid, on Spinal Cord Injury-Induced Motor Dysfunction in Rats

“…It has been reported to inhibit collageninduced arthritis in mice, as well as experimental allergic encephalomyelitis and other conditions. [15][16][17][18][19] Am-80 shows approximately 10-fold stronger promotion of the differentiation of HL-60 cells 20) than ATRA. Different from ATRA, it acts by binding to the RARa and RARb, but not RARg.…”

Oral Administration of Synthetic Retinoid Am80 Inhibits the Development of Type 1 Diabetes in Non-obese Diabetic (NOD) Mice

“…Am80 has been reported to inhibit the development of collagen-induced arthritis in mice and rats, experimental autoimmune encephalomyelitis in rats and 2,4-dinitrofluorobenzene-induced contact dermatitis in mice. [9][10][11][12] In this study we examined the effect of Am80 administration on the development of type 1 diabetes in NOD mice in order to clarify its immunomodulatory competence.…”