Up-regulation of transforming growth factor alpha binding sites in experimental rabbit colitis

Transforming growth factor alpha (TGF-alpha), a member of the epidermal growth factor family, has been proposed to mediate protection against mucosal injury and promote healing of the gastrointestinal mucosa. TGF-alpha acts via a plasma membrane receptor, which is distributed throughout the digestive system with the highest density in epithelia. The aim of this study was to investigate the pattern of TGF-alpha binding sites in the normal and inflamed rabbit colon.

The immune complex/formalin model of acute colitis and tissue section receptor autoradiography were used. Inflammation was characterized by cellular infiltration, edema, and necrosis. TGF-alpha binding relative density was determined by densitometry on film autoradiograms.

The normal colon had a low to moderate density of specific TGF-alpha binding sites in the mucosa and external muscle. TGF-alpha binding density was significantly increased in the mucosa at 4 hours and remained higher than normal for up to 48 hours. The density of binding sites in the mucosa and the inflammatory index returned to near normal values at 96 hours, when colitis had subsided.

The increase in TGF-alpha binding in the mucosa during experimental colitis supports the hypothesis that members of the epidermal growth factor family play a role in inflammation, perhaps acting as mediators of mucosal protection and repair.