Human neutrophil peptide‐1 aggravates dextran sulfate sodium‐induced colitis

• Published in: Inflammatory bowel diseases Vol. 18; no. 4; pp. 667 - 675
• Main Authors: Hashimoto, Shinichi, Uto, Hirofumi, Kanmura, Shuji, Sakiyama, Toshio, Oku, Manei, Iwashita, Yuji, Ibusuki, Rie, Sasaki, Fumisato, Ibusuki, Kazunari, Takami, Yoichiro, Moriuchi, Akihiro, Oketani, Makoto, Ido, Akio, Tsubouchi, Hirohito
• Format: Journal Article
• Language: English
• Published: Hoboken Wiley Subscription Services, Inc., A Wiley Company 01-04-2012
• Subjects: alpha-Defensins - adverse effects; Animals; Cells, Cultured; Colitis - chemically induced; Colitis - metabolism; Colitis - pathology; Colon - anatomy & histology; Colon - drug effects; Colon - metabolism; Colon - pathology; Dextran Sulfate - toxicity; dextran sulfate sodium; Disease Models, Animal; human neutrophil peptide‐1; Humans; IL‐1β; Interferon-gamma - secretion; Interleukin-1beta - biosynthesis; Intestinal Mucosa - drug effects; Intestinal Mucosa - metabolism; Intestinal Mucosa - pathology; macrophage; Macrophages - drug effects; Macrophages - metabolism; Male; Mice; Mice, Inbred BALB C; Mice, SCID; Peroxidase - analysis; Severity of Illness Index; Tumor Necrosis Factor-alpha - secretion; ulcerative colitis; Up-Regulation
• ISSN: 1078-0998; 1536-4844
• DOI: 10.1002/ibd.21855

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)‐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.
Conclusions:
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;)