E. Ierardi1, F. Giorgio1, D. Piscitelli2, M. Fiore1, R. Rossi1, S. Cantatore1, M. Principi2, A. Di Leo2, C. Panella1, 1University of Foggia, 2University of Bari, Bari, Italy
Tumor necrosis factor (TNF) alpha downregulation by infliximab therapy may induce mucosal healing interacting with syndecan 1/basic fibroblast growth factor (bFGF) link, which play a key role in tissue repair. Aim of the present work was to investigate whether a dysregulation of the balance of these three molecules could indicate a pattern for the stenotic complication of Crohn's disease.
Our study was performed on surgical specimens from 24 patients undergoing intestinal resection for fibrotic stenosis. Ten histological normal surgical samples were respectively retrieved for both the large and small bowel from patients with different conditions (large adenomas, hernia, diverticula, volvulus). Strikingly, healthy surrounding diseased tissue was taken and represented the control collection, who did not differ for sex and age distribution from the Crohn's disease group. Additionally, 3 endoscopic biopsy specimens taken after informed consent in subjects undergoing colonoscopy for intestinal cancer familiarity were used as negative controls in each assay. TNF alpha, syndecan 1 and bFGF were detected by both reverse transcriptase RT-PCR after mRNA extraction (results expressed as fold-change) and immunohistochemistry.
The levels of TNF alpha did not show a significant difference from that observed in normal tissue (1.54±1.19; n. s.). However, very high levels of bFGF were observed in Crohn's disease (11.76±4.65; p < 0.001), while syndecan 1 showed a moderate increase, as characteristic of inflamed tissue (5.53±2.18; p < 0.005). ANOVA plus Student-Neumann-Keuls showed: bFGF > syndecan 1 > TNF alpha = control. Immunoreactivity for bFGF was observed in epithelial, stromal (fibroblasts, myofibroblasts, monocytes, macrophages and neutrophils) and endothelial cells and even in the muscular lawyer. Syndecan 1 and TNF alpha staining was confined to mucosa.
Our results suggest that fibrotic stenosis of Crohn's disease may be the final result of an irreversible transformation of different type of cells into the fibrogenetic phenotype, thus provoking the prevalence of fibrotic on inflammatory stenotic lesions. During this process the exceeding of extracellular matrix is the result of a failure of the modulation of bFGF by syndecan1.