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Dig Dis Sci. 2014 Apr;59(4):760-8. doi: 10.1007/s10620-013-2813-8. Epub 2013 Aug 22.

Fibrocytes are involved in inflammation as well as fibrosis in the pathogenesis of Crohn's disease.

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  • 1Department of Gastroenterology and Nephrology (K1), Graduate School of Medicine, Chiba University, 1-8-1 Inohana, Chuo-ku, Chiba-shi, 260-8670, Japan.

Abstract

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.

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PMID:
23975339
[PubMed - indexed for MEDLINE]
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