Modulation of immunological responses and amelioration of collagen-induced arthritis by the novel roxithromycin derivative 5-I.
Mod Rheumatol
; 25(4): 562-70, 2015 Jul.
Article
em En
| MEDLINE
| ID: mdl-25800509
ABSTRACT
OBJECTIVE:
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. Importantly, administration of 5-I to mice with collagen-induced arthritis reduced the severity of arthritis, and this effect was also observed when treatment was delayed till after the onset of disease.CONCLUSION:
Our findings strongly suggest that 5-I may be useful as a potential therapeutic agent for human rheumatoid arthritis.Palavras-chave
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Artrite Experimental
/
Artrite Reumatoide
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Roxitromicina
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Linfócitos T Auxiliares-Indutores
/
Imunidade Celular
Tipo de estudo:
Prognostic_studies
Limite:
Animals
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Humans
/
Male
Idioma:
En
Ano de publicação:
2015
Tipo de documento:
Article