Journal
INFLAMMATORY BOWEL DISEASES
Volume 18, Issue 4, Pages 667-675Publisher
OXFORD UNIV PRESS INC
DOI: 10.1002/ibd.21855
Keywords
human neutrophil peptide-1; ulcerative colitis; dextran sulfate sodium; macrophage; IL-1 ss
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Funding
- Ministry of Education, Culture, Sports, Science and Technology of Japan
- Ministry of Health, Labour and Welfare of Japan
- Grants-in-Aid for Scientific Research [23249043] Funding Source: KAKEN
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Background: Human neutrophil peptide (HNP)-1, HNP-2, and HNP-3 (HNP-13) 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 mu g/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-gamma and tumor necrosis factor-a levels in colon culture supernatants-derived HNP-1-treated mice were also significantly higher, and interleukin (IL)-1 beta levels tended to increase in response to HNP-1. In addition, treating SCID mice with HNP-1 aggravated DSS-induced colitis and IL-1 beta 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-1 beta. These results indicate that high concentrations of HNP-1-3 in patients with UC may exacerbate disease activity via increased cytokine production.
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