Human neutrophil peptide-1 aggravates dextran sulfate sodium-induced colitis.
Inflamm Bowel Dis
; 18(4): 667-75, 2012 Apr.
Article
em En
| MEDLINE
| ID: mdl-21928371
ABSTRACT
BACKGROUND:
Human neutrophil peptide (HNP)-1, HNP-2, and HNP-3 (HNP-1-3) are useful biomarkers for ulcerative colitis (UC). The precise roles of these peptides in UC are poorly understood, however. The aim of this study was to determine whether HNP-1 affects disease activity in mice with experimental colitis.METHODS:
Experimental colitis was induced in BALB/c or severe combined immunodeficiency (SCID) mice using dextran sulfate sodium (DSS). Mice were subsequently treated intraperitoneally with HNP-1 (100 µg/day) or phosphate-buffered saline (PBS) from day 4 to day 6. The severity of colitis was evaluated based on a disease activity index, histologic score, and cytokine expression.RESULTS:
Body weight and colon length significantly decreased and the disease activity index score, histologic score, and myeloperoxidase activity significantly increased in HNP-1-treated BALB/c mice compared with PBS-treated mice. Interferon-γ and tumor necrosis factor-α levels in colon culture supernatants-derived HNP-1-treated mice were also significantly higher, and interleukin (IL)-1ß levels tended to increase in response to HNP-1. In addition, treating SCID mice with HNP-1 aggravated DSS-induced colitis and IL-1ß levels in colon culture supernatants from these mice were significantly higher than in cultures obtained from control mice. Furthermore, in both BALB/c and SCID mice increased recruitment of F4/80-positive macrophages was observed in the inflamed colonic mucosa following HNP-1 injections.CONCLUSIONS:
High concentrations of HNP-1 aggravate DSS-induced colitis, including upregulated expression of such macrophage-derived cytokines as IL-1ß. These results indicate that high concentrations of HNP-1-3 in patients with UC may exacerbate disease activity via increased cytokine production.
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Colite
/
Colo
/
Alfa-Defensinas
/
Mucosa Intestinal
Tipo de estudo:
Prognostic_studies
Limite:
Animals
/
Humans
/
Male
Idioma:
En
Revista:
Inflamm Bowel Dis
Assunto da revista:
GASTROENTEROLOGIA
Ano de publicação:
2012
Tipo de documento:
Article
País de afiliação:
Japão