Supported in part by grants from the Ministry of Education, Culture, Sports, Science and Technology of Japan, and the Ministry of Health, Labour and Welfare of Japan.
Human neutrophil peptide-1 aggravates dextran sulfate sodium-induced colitis†
Article first published online: 16 SEP 2011
Copyright © 2011 Crohn's & Colitis Foundation of America, Inc.
Inflammatory Bowel Diseases
Volume 18, Issue 4, pages 667–675, April 2012
How to Cite
Hashimoto, S., Uto, H., Kanmura, S., Sakiyama, T., Oku, M., Iwashita, Y., Ibusuki, R., Sasaki, F., Ibusuki, K., Takami, Y., Moriuchi, A., Oketani, M., Ido, A. and Tsubouchi, H. (2012), Human neutrophil peptide-1 aggravates dextran sulfate sodium-induced colitis. Inflamm Bowel Dis, 18: 667–675. doi: 10.1002/ibd.21855
- Issue published online: 19 MAR 2012
- Article first published online: 16 SEP 2011
- Manuscript Accepted: 18 JUL 2011
- Manuscript Received: 14 JUL 2011
- human neutrophil peptide-1;
- ulcerative colitis;
- dextran sulfate sodium;
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.
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.
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)-1β levels tended to increase in response to HNP-1. In addition, treating SCID mice with HNP-1 aggravated DSS-induced colitis and IL-1β 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.
High concentrations of HNP-1 aggravate DSS-induced colitis, including upregulated expression of such macrophage-derived cytokines as IL-1β. These results indicate that high concentrations of HNP-1–3 in patients with UC may exacerbate disease activity via increased cytokine production. (Inflamm Bowel Dis 2011;)