Am80, a retinoic acid receptor agonist, ameliorates murine vasculitis through the suppression of neutrophil migration and activation

Abstract

Objective. Vasculitis is characterized by leukocyte infiltration in the vessel walls, with destructive damage to mural structures. Retinoids are compounds that bind to retinoic acid receptors and exert biologic activities similar to those of vitamin A, including modulatory effects on cell proliferation and differentiation. This study was undertaken to examine the therapeutic effects of a synthetic retinoid, Am80, in a murine model of vasculitis induced by Candida albicans water-soluble fraction (CAWS). Vasculitis is defined by the presence of inflammatory leukocytes in vessel walls, with destructive damage to mural structures. Antineutrophil cytoplasmic antibodies are often detected in certain types of vasculitis, such as microscopic polyangiitis. The affected vessels vary in size, type, and location according to the type of vasculitic disease (1). Although the exact mechanisms

Retinoic acid receptor stimulation ameliorates experimental autoimmune optic neuritis

“…The results of recent studies have shown that Am80 is capable of suppressing experimental autoimmune diseases and chronic graft-versus-host disease. [19][20][21][22] We have also demonstrated that treatment by Am80 ameliorates experimental autoimmune uveoretinitis during the entire phase of the disease. 23 Am80 is a RAR α/β-selective retinoid that dose not bind and activate RAR-γ and RXRs, hence can reduce the unfa-vourable adverse effects.…”

β-mannosyl linkages inhibit CAWS arteritis by negatively regulating dectin-2-dependent signaling in spleen and dendritic cells

“…Therefore, neutrophils play an important role in CAWS-vasculitis and exhibit the characteristics of neutrophils such as (i) prolonged survival in inflammatory tissue, (ii) the production of a variety of inflammatory and tissue mediators in blood vessels, such as reactive oxygen species, arachidonate metabolites, proteases and glycosidases, are strongly related to the degradation and remodeling of blood vessels 36,37 . Furthermore, we found that CCR2, a receptor for MCP-1, deficient mice were resistant to CAWS-vasculitis 10 .…”

Aetiological Significance of Infectious Stimuli in Kawasaki Disease

“…KD-like vasculitis can be induced in rabbit, swine, and mouse models by various methods (80)(81)(82)(83). The known genetic background and ease of genetic manipulation have made mouse models the preferred model to investigate molecular pathogenesis of KD and to discover its therapeutic targets (84)(85)(86)(87)(88).…”