Modulation of immunological responses and amelioration of collagen-induced arthritis by the novel roxithromycin derivative 5-I
2015
AbstractObjective: Macrolide antibiotics have immunomodulatory properties that are distinct from their antibacterial functions. We synthesized 5-I, which is a new derivative of RXM with less antimicrobial activity, and evaluated its immunomodulatory effects through both in vitro and in vivo studies.Methods: Proliferative response, cytokine production, and expression of mRNA of T cells stimulated with anti-CD3 and anti-CD28 mAbs in the presence or absence of monocytes, cytokine production of monocytes stimulated with lipopolysaccharide, and transendothelial migration of T cells in various concentrations of 5-I were analyzed. The effect of 5-I treatment was also evaluated in a mouse model of collagen-induced arthritis.Results: 5-I specifically inhibited production of Th1, Th17, and proinflammatory cytokines such as IL-2, IFN-γ, TNF-α, IL-6, and IL-17A. 5-I reduced the expression of RORC on CD4+ T cells, which codes for RORγt, the master regulator of Th17, and it also inhibited migration of activated T cells...
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