Human cathelicidin LL-37-derived peptide IG-19 confers protection in a murine model of collagen-induced arthritis.
Mol Immunol
; 57(2): 86-92, 2014 Feb.
Article
em En
| MEDLINE
| ID: mdl-24091294
ABSTRACT
Current therapies for autoimmune chronic inflammatory diseases e.g. rheumatoid arthritis (RA) include inhibitors of inflammatory cytokines. However, these therapies can result in increased risk of infections. There is a need to explore alternate strategies that can control inflammation without compromising the innate ability to resolve infections. In this study, we examined the effect of small peptides derived from endogenous cathelicidin peptides in a murine model of collagen-induced arthritis (CIA). Cathelicidins are immunomodulatory peptides known to control infections. We demonstrate that the administration of the peptide IG-19, which represents an internal segment of the human cathelicidin LL-37, decreased disease severity and significantly reduced the serum levels of antibodies against collagen type II in the CIA model. IG-19 peptide reduced cellular infiltration in joints, prevented cartilage degradation and suppressed pro-inflammatory cytokines in the CIA mice. We also showed that not all cathelicidin-derived peptides exhibit similar functions. A bovine cathelicidin-derived peptide IDR-1018 did not exhibit the beneficial effects observed with the human cathelicidin LL-37-derived peptide IG-19, in the same murine model of CIA. This is the first study to provide evidence demonstrating the ability of a peptide derived from the human cathelicidin LL-37 to alleviate the arthritic disease process in a murine model of RA. Our results has lead us to propose a new approach for controlling autoimmune chronic inflammatory disorders such as RA, by using specific synthetic derivatives of endogenous host defence peptides. Cathelicidin-derived peptides are particularly attractive for their dual antimicrobial and anti-inflammatory actions.
Palavras-chave
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Artrite Experimental
/
Anti-Inflamatórios não Esteroides
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Citocinas
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Peptídeos Catiônicos Antimicrobianos
Limite:
Animals
Idioma:
En
Revista:
Mol Immunol
Ano de publicação:
2014
Tipo de documento:
Article
País de afiliação:
Canadá