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. 1999 May;44(5):636-42.
doi: 10.1136/gut.44.5.636.

Trefoil peptide TFF2 (spasmolytic polypeptide) potently accelerates healing and reduces inflammation in a rat model of colitis

C P Tran  1 , G A Cook, N D Yeomans, L Thim, A S Giraud
Affiliations

Trefoil peptide TFF2 (spasmolytic polypeptide) potently accelerates healing and reduces inflammation in a rat model of colitis

C P Tran et al. Gut. 1999 May.

Abstract

Background: The trefoil peptides are major secretory products of mucus cells of the gastrointestinal tract and show increased expression after inflammatory or ulcerative damage. Recombinant human TFF2 (spasmolytic polypeptide) has been shown to be cytoprotective, and enhances repair in models of gastric injury.

Aims: To test the healing effects of recombinant human (h)TFF2 in a rat model of chronic colitis.

Methods: Colitis was induced by intracolonic administration of dinitrobenzene sulphonic acid in ethanol. Mucosal repair was quantified macroscopically, microscopically by image analysis of tissue histology, and by measuring myeloperoxidase activity.

Results: Initial validation studies showed that maximal injury and inflammation occurred at the end of the first week after colitis induction (active phase), and that spontaneous healing was complete by eight weeks. Once daily intrarectal application of hTFF2 (2.5 mg/kg; approximately 0.5 mg/rat) for five days after maximal damage had been sustained, reduced both microscopic and macroscopic injury by 80% and inflammatory index by 50% compared with vehicle controls. In addition, endogenous concentrations of rat TFF2 and TFF3 (intestinal trefoil factor) were increased in the active phase of colitis and were reduced to basal levels by hTFF2 treatment.

Conclusions: This study has shown that hTFF2 enhances the rate of colonic epithelial repair, and reduces local inflammation in a rat model of colitis, and suggests that luminal application of trefoil peptides may have therapeutic potential in the treatment of inflammatory bowel disease.

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Figures

Figure 1
Figure 1
Schematic representation of the time course of DNBS/ethanol induced colitis and resolution (protocol A), and the TFF2 healing study (protocol B).
Figure 2
Figure 2
Macroscopic (A; graded point scale) and microscopic (B; ratio of the length of epithelial damage to total section length) damage quantitation in control rats or rats with colitis. *p=0.006, †p<0.02.
Figure 3
Figure 3
Haematoxylin and eosin stained histological sections of rat colonic mucosa from the time course study. (A) Saline control, (B) one week, (C) two weeks, (D) eight weeks after colitis induction. Ulceration is indicated by arrows. Original magnification × 16.
Figure 4
Figure 4
Time course quantitation of the microscopic cross sectional area of mucosal compartment damage after DNBS/ethanol colitis induction, expressed as a percentage of the total cross sectional area of histological sections of epithelium (A) and lamina propria (B); (C) myeloperoxidase (MPO) activity after DNBS/ethanol colitis.
Figure 5
Figure 5
Tissue concentrations of the endogenous trefoil peptides TFF3 (A) and TFF2 (B) after induction of colitis by DNBS/ethanol.
Figure 6
Figure 6
Histological sections of rat colonic mucosa six days after DNBS/ethanol colitis induction and treatment for five days with methylcellulose (A,B) or TFF2 (C,D). Sections stained with haematoxylin and eosin. Areas of erosion and gross inflammatory cell infiltrate are arrowed. Original magnification × 16.
Figure 7
Figure 7
Quantitation of (A) macroscopic colitis score and (B) microscopic cellular damage expressed as a ratio of the length of epithelial damage to total histological section length after DNBS/ethanol colitis and treatment with vehicle or TFF2. MC, methylcellulose.
Figure 8
Figure 8
Effect of vehicle (methylcellulose; MC) or TFF2 on the microscopic cross sectional area of mucosal compartment damage after DNBS/ethanol colitis induction, expressed as a percentage of the total cross sectional area of histological sections of epithelium (A) or lamina propria (B); (C) mucosal myeloperoxidase (MPO) activity.
Figure 9
Figure 9
Effect of vehicle (methylcellulose; MC) or TFF2 on endogenous mucosal TFF2 and TFF3 concentrations after DNBS/ethanol colitis induction.
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