Hepcidin expression in colon during trinitrobenzene sulfonic acid-induced colitis in rats

Autor(es)

Ferreira Gotardo, Erica Martins ^[1] ; Ribeiro, Gilberto de Almeida ^[1] ; Leite Clemente, Thayane Rodrigues ^[1] ; Moscato, Camila Henrique ^[1] ; Guerra Tome, Renata Bortolin ^[1] ; Rocha, Thalita ^[1] ; Pedrazzoli, Jr., Jose ^[1] ; Ribeiro, Marcelo Lima ^[1] ; Gambero, Alessandra ^[1]

Afiliação do(s) autor(es)

^[1] Univ Sao Francisco, Sch Med, Clin Pharmacol & Gastroenterol Unit, BR-12916900 Braganca Paulista, SP - Brazil

• Tipo de documento: Artigo Científico
• Fonte: WORLD JOURNAL OF GASTROENTEROLOGY; v. 20, n. 15, p. 4345-4352, APR 21 2014.
• Citações Web of Science: 2

Resumo

AIM: To investigate hepcidin expression, interleukin-6 (IL-6) production and iron levels in the rat colon in the presence of trinitrobenzene sulfonic acid (TNBS)-induced colitis. METHODS: In rats, we evaluated the severity of colitis induced by repeated TNBS administration using macroscopic and microscopic scoring systems and myeloperoxidase activity measurements. The colonic levels of hepcidin, tumor necrosis factor alpha (TNF-alpha), IL-10 and IL-6 were measured by Enzyme-Linked Immunosorbent Assay, and hepcidin-25 expression and iron deposition were analyzed by immunohistochemistry and the Prussian blue reaction, respectively. Stat-3 phosphorylation was assessed by Western blot analysis. Hematological parameters, iron and transferrin levels, and transferrin saturation were also measured. Additionally, the ability of iron, pathogen-derived molecules and IL-6 to induce hepcidin expression in HT-29 cells was evaluated. RESULTS: Repeated TNBS administration to rats resulted in macroscopically and microscopically detectable colon lesions and elevated colonic myeloperoxidase activity. Hepcidin-25 protein levels were increased in colonic surface epithelia in colitic rats (10.2 +/- 4.0 pg/mg protein vs 71.0 +/- 8.4 pg/mg protein, P < 0.01). Elevated IL-6 levels (8.2 +/- 1.7 pg/mg protein vs 14.7 +/- 0.7 pg/mg protein, P < 0.05), TNF-alpha levels (1.8 +/- 1.2 pg/mg protein vs 7.4 +/- 2.1 pg/mg protein, P < 0.05) and Stat-3 phosphorylation were also observed. Systemic alterations in iron homeostasis, hepcidin levels and anemia were not detected in colitic rats. Iron deposition in the colon was only observed during colitis. Hepcidin gene expression was increased in HT-29 cells after IL-6 and lipopolysaccharide {[} a toll-like receptor 4 (TLR-4) ligand] treatment. Deferoxamine, ferric citrate and peptidoglycan (a TLR-2 ligand) were unable to alter the in vitro expression of hepcidin in HT-29 cells. CONCLUSION: Colitis increased local hepcidin-25 expression, which was associated with the IL-6/Stat-3 signaling pathway. An increase in local iron sequestration was also observed, but additional studies are needed to determine whether this sequestration is a defensive or pathological response to intestinal inflammation. (C) 2014 Baishideng Publishing Group Co., Limited. All rights reserved. (AU)

• Processo FAPESP: 10/02991-6 - Avaliação da participação da apelina e hepcidina na inflamação intestinal e nas alterações do tecido adiposo mesentérico.
• Beneficiário: Alessandra Gambero
• Modalidade de apoio: Auxílio à Pesquisa - Regular