Human neutrophil peptide-1 aggravates dextran sulfate sodium-induced colitis.

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)-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.

• Authors: Shinichi Hashimoto, Hirofumi Uto, Shuji Kanmura, Toshio Sakiyama, Manei Oku, Yuji Iwashita, Rie Ibusuki, Fumisato Sasaki, Kazunari Ibusuki, Yoichiro Takami, Akihiro Moriuchi, Makoto Oketani, Akio Ido, Hirohito Tsubouchi
• Journal: Inflammatory bowel diseases (Inflamm Bowel Dis) Vol. 18 Issue 4 Pg. 667-75 (Apr 2012) ISSN: 1536-4844 [Electronic] England
• PMID: 21928371 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2011 Crohn's & Colitis Foundation of America, Inc.

Chemical References

• Interleukin-1beta
• Tumor Necrosis Factor-alpha
• alpha-Defensins
• human neutrophil peptide 1
• Interferon-gamma
• Dextran Sulfate
• Peroxidase

Topics

• Animals
• Cells, Cultured
• Colitis (chemically induced, metabolism, pathology)
• Colon (anatomy & histology, drug effects, metabolism, pathology)
• Dextran Sulfate (toxicity)
• Disease Models, Animal
• Humans
• Interferon-gamma (metabolism)
• Interleukin-1beta (biosynthesis)
• Intestinal Mucosa (drug effects, metabolism, pathology)
• Macrophages (drug effects, metabolism)
• Male
• Mice
• Mice, Inbred BALB C
• Mice, SCID
• Peroxidase (analysis)
• Severity of Illness Index
• Tumor Necrosis Factor-alpha (metabolism)
• Up-Regulation
• alpha-Defensins (adverse effects)