D. Beddy

Increased vascular endothelial growth factor production in fibroblasts isolated from strictures in patients with Crohn's disease†

Vascular endothelial growth factor (VEGF) is a potent angiogenic factor that is implicated in early wound healing and fibrosis. Fibroblasts may initiate stricture formation in Crohns disease through overexpression of VEGF. The aim of this study was to examine VEGF expression and regulation in fibroblasts isolated from patients with Crohns disease.

Increased Adhesion Molecule Expression in Serosal Fibroblasts Isolated From Patients with Inflammatory Bowel Disease is Secondary to Inflammation

ObjectiveTo examine the expression of adhesion molecules by serosal and dermal fibroblasts in patients with inflammatory bowel disease. Summary Background DataThe pathophysiologic process that leads to stricture formation in Crohn’s disease (CD) is unknown. Serosal fibroblasts in these patients have an enhanced ability to contract collagen. This property may be reflected in fibroblast adhesion molecule expression, which in turn may be constitutive or secondary to the inflammatory process in patients with CD. MethodsFibroblasts were isolated from inflamed and macroscopically normal serosa of patients with CD or ulcerative colitis (UC) and from normal serosa of patients with colon cancer. Dermal fibroblasts were also isolated from the wound edge. Cell surface and whole cell expression of ICAM-1 were evaluated by flow cytometry and Western blot analysis, respectively. NF&kgr;B was measured by mobility shift assay in parallel experiments. Interleukin 1&bgr; was added to the culture medium. ResultsExpression of ICAM-1 and NF&kgr;B, increased in patients with both CD and UC, was unaltered by interleukin 1&bgr;. The whole cell concentration of ICAM-1 was greater in patients with CD than in patients with UC. Dermal fibroblasts did not display these features. ConclusionsPatients with inflammatory bowel disease display enhanced ICAM-1 expression in serosal fibroblasts but not dermal fibroblasts, indicating a secondary response to inflammation.

Author's reply: Increased vascular endothelial growth factor production in fibroblasts isolated from strictures in patients with Crohn's disease (Br J Surg 2004; 91: 72-77)

Sir There is abundant evidence that Crohn’s disease is associated with smoking1 and the resulting ischaemia is said to be a possible mechanism for Crohn’s recurrence2. This paper suggests that increased fibroblast vascular endothelial growth factor (VEGF) production may play a role in initiating Crohn’s strictures; it would be interesting for the authors to explore whether ischaemia, which is known to upregulate VEGF3, explains this relationship. The authors go on to suggest that steroids may reduce fibrosis in Crohn’s disease by reducing VEGF production. It is thus tempting to hypothesise that since other agents used in the treatment of Crohn’s are also anti-angiogenic4, VEGF inhibition may be a mechanism common to Crohn’s treatments. G.F. Nash Department of Surgery, St Mark’s Hospital, Watford Road, Harrow, Middlesex HA1 3UJ, UK DOI: 10.1002/bjs.4655

Critical involvement of stress-activated MAP kinases in the regulation of fibroblast ICAM-1 expression in Crohn’s disease

ConclusionsTNF-α and IL-lβ up-regulate ICAM-1 expression in serosal fibroblasts through the activation of the JUN kinase signalling pathway. Specific inhibition of inflammatory signalling pathways could provide novel therapeutic targets for the treatment of Crohn’s disease.