title: 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.affiliation: Department of Digestive and Lifestyle Related Disease, Health Research Course, Human and Environmental Sciences, Kagoshima University Graduate School of Medical and Dental Sciences, Kagoshima, Japan.
authors.forename: Shinichi
authors.initials: S
authors.lastname: Hashimoto
authors.forename: Hirofumi
authors.initials: H
authors.lastname: Uto
authors.forename: Shuji
authors.initials: S
authors.lastname: Kanmura
authors.forename: Toshio
authors.initials: T
authors.lastname: Sakiyama
authors.forename: Manei
authors.initials: M
authors.lastname: Oku
authors.forename: Yuji
authors.initials: Y
authors.lastname: Iwashita
authors.forename: Rie
authors.initials: R
authors.lastname: Ibusuki
authors.forename: Fumisato
authors.initials: F
authors.lastname: Sasaki
authors.forename: Kazunari
authors.initials: K
authors.lastname: Ibusuki
authors.forename: Yoichiro
authors.initials: Y
authors.lastname: Takami
authors.forename: Akihiro
authors.initials: A
authors.lastname: Moriuchi
authors.forename: Makoto
authors.initials: M
authors.lastname: Oketani
authors.forename: Akio
authors.initials: A
authors.lastname: Ido
authors.forename: Hirohito
authors.initials: H
authors.lastname: Tsubouchi
mesh_terms: D000818:Animals; D002478:Cells, Cultured; D003092:Colitis / Q000139:chemically induced / Q000378:metabolism* / Q000473:pathology; D003106:Colon / Q000033:anatomy & histology / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D016264:Dextran Sulfate / Q000633:toxicity; D004195:Disease Models, Animal; D006801:Humans; D007371:Interferon-gamma / Q000378:metabolism; D053583:Interleukin-1beta / Q000096:biosynthesis; D007413:Intestinal Mucosa / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D008264:Macrophages / Q000187:drug effects / Q000378:metabolism; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D016513:Mice, SCID; D009195:Peroxidase / Q000032:analysis; D012720:Severity of Illness Index; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism; D015854:Up-Regulation; D023084:alpha-Defensins / Q000009:adverse effects*
chemical_list: D053583:Interleukin-1beta; D014409:Tumor Necrosis Factor-alpha; D023084:alpha-Defensins; C406413:human neutrophil peptide 1; D007371:Interferon-gamma; D016264:Dextran Sulfate; D009195:Peroxidase