Background: We previously showed that fibrocytes, a hematopoietic stem cell source of fibroblasts/myofibroblasts, infiltrated the colonic mucosa of a murine colitis model. Aim: We investigated whether fibrocytes were involved in the pathogenesis of Crohn's disease. Methods: Human surgical intestinal specimens were stained with anti-leukocyte-specific protein 1 and anti-collagen type-I (ColI) antibodies. Circulating fibrocytes in the human peripheral blood were quantified by fluorescence-activated cell sorting with anti-CD45 and anti-ColI antibodies. Cultured human fibrocytes were prepared by culturing peripheral CD14+ monocytes. Results: In the specimens of patients with Crohn's disease, the fibrocyte/total leukocyte percentage was significantly increased in inflammatory lesions (22.2 %, p < 0.01) compared with that in non-affected areas of the intestine (2.5 %). Interestingly, the percentage in fibrotic lesions was similar (2.2 %, p = 0.87) to that in non-affected areas. The percentages of circulating fibrocytes/total leukocytes were significantly higher in patients with Crohn's disease than in healthy controls. Both CXC-chemokine receptor 4+ and intercellular adhesion molecule 1 + fibrocyte numbers were significantly increased in Crohn's disease, suggesting that circulating fibrocytes have a higher ability to infiltrate injured sites and traffic leukocytes. In cultured fibrocytes, lipopolysaccharide treatment remarkably upregulated tumor necrosis factor (TNF)-α mRNA (17.0 ± 5.7-fold) and ColI mRNA expression (12.8 ± 5.7-fold), indicating that fibrocytes stimulated by bacterial components directly augmented inflammation as well as fibrosis. Conclusions: Fibrocytes are recruited early in the inflammatory phase and likely differentiate into fibroblasts/ myofibroblasts until the fibrosis phase. They may enhance inflammation by producing TNF-α and can directly augment fibrosis by producing ColI. © 2013 Springer Science+Business Media.
CITATION STYLE
Sazuka, S., Katsuno, T., Nakagawa, T., Saito, M., Saito, K., Maruoka, D., … Yokosuka, O. (2014). Fibrocytes are involved in inflammation as well as fibrosis in the pathogenesis of Crohn’s disease. Digestive Diseases and Sciences, 59(4), 760–768. https://doi.org/10.1007/s10620-013-2813-8
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