RESUMEN
Fibrocytes contribute to wound healing and are uniquely defined by coexpression of hematopoietic and mesenchymal cell markers. In this study, trafficking of fibrocytes was determined in a murine model of colitis induced by administering 3% dextran sodium sulfate (DSS) for seven days. Colonic tissues were immunostained for CD45, collagen type I (Col I), and alpha-SMA. On day 0, there were no CD45(+)Col I(+) cells in colonic tissues. However, on day 7 when inflammatory cells showed remarkable accumulation, oval-shaped CD45(+)Col I(+) fibrocytes were obvious in the submucosal layer. On day 14 when colonic tissues were in the healing phase, numerous spindle-shaped CD45(+)Col I(+) fibrocytes were observed. Emergence of CD45(+)Col I(+) fibrocytes preceded the appearance of alpha-SMA(+) myofibroblasts. Oval-shaped fibrocytes recruited as early as the inflammatory phase of colitis are likely to differentiate into spindle-shaped fibrocytes in the healing phase, suggesting that fibrocytes may promote wound healing in inflamed colonic tissues.
Asunto(s)
Colitis/patología , Fibroblastos/patología , Actinas/metabolismo , Animales , Colitis/inmunología , Colitis/metabolismo , Colágeno Tipo I/metabolismo , Modelos Animales de Enfermedad , Progresión de la Enfermedad , Fibroblastos/inmunología , Fibroblastos/metabolismo , Estudios de Seguimiento , Inmunohistoquímica , Mucosa Intestinal/inmunología , Mucosa Intestinal/metabolismo , Mucosa Intestinal/patología , Antígenos Comunes de Leucocito/metabolismo , Masculino , Ratones , Ratones Endogámicos BALB C , Microscopía ConfocalRESUMEN
The present study was performed to examine whether probiotics affect Toll-like receptor 4 (TLR4) expression in human colonic epithelial cells. Culture supernatants or heat-killed bacteria of Bacillus mesentericus TO-A, Clostridium butyricum TO-A, and Streptococcus faecalis T-110 were applied to human colonic epithelial cells. Treatment with C. butyricum TO-A culture supernatant significantly reduced TLR4 mRNA level (x0.16), even in the presence of interferon-gamma (IFN-gamma; x0.21) as compared with untreated controls. High-performance liquid chromatography analysis showed that C. butyricum TO-A supernatant contains formate, acetate, and butyrate. Interestingly, TLR4 mRNA was significantly suppressed (x0.15-x0.22) only when cells were treated with solutions containing butyrate. Electrophoretic mobility shift assay suggested that the binding affinity of PU.1 to the promoter region of the TLR4 gene was markedly inhibited when the cells were treated with butyrate. This study suggested that butyrate produced by C. butyricum TO-A downregulates TLR4 mRNA level in human colonic epithelial cells.