Fasciola helminth defense molecule-1 protects against experimental arthritis by inhibiting osteoclast formation and function without modulating the systemic immune response.
FASEB J
; 34(1): 1091-1106, 2020 01.
Article
em En
| MEDLINE
| ID: mdl-31914677
ABSTRACT
An inverse correlation between helminth infection and the autoimmune disease appears to be contributed by the anti-inflammatory factors produced by these organisms. Suppressing osteoclast function without affecting the systemic immunological response is an emerging therapeutic strategy for rheumatoid arthritis (RA). We observed that a synthetic peptide corresponding to 34 amino acids of C-terminal sequence of Fasciola helminth defense molecule-1 (C-FhHDM-1) inhibited RANKL-induced osteoclast formation and lysosomal acidification with an attendant upregulation of sequestome1/p62, a negative regulator of NF-κB expression. C-FhHDM-1 also suppressed RANKL production from osteoblasts. Macrophages are the major inflammatory cells in the joints of RA and C-FhHDM-1 suppressed ICAM-1 (an inflammatory surrogate) expression in these cells. In a murine model of collagen II-induced arthritis (CIA), C-FhHDM-1 improved clinical score, protected against cartilage destruction, and maintained bone mass and bone architecture of joints compared with the CIA group. C-FhHDM-1 suppressed the CIA-induced expression of TNF, IL-17, and IFN-γ in joints but not their serum levels. The peptide also had no effect on the CIA-induced suppression of T regulatory response. We conclude that C-FhHDM-1 has a joint-specific protective effect in experimental arthritis without mitigating systemic inflammation, and thus could become an adjuvant anti-arthritis therapy to prevent RA-induced osteopenia.
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Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Osteoclastos
/
Peptídeos
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Artrite Experimental
Tipo de estudo:
Prognostic_studies
Limite:
Animals
Idioma:
En
Ano de publicação:
2020
Tipo de documento:
Article