Differing patterns of transforming growth factor-beta expression in normalintestinal mucosa and in active celiac disease

Background: Growth-inhibitory autocrine polypeptides such as transforming g rowth factor (TGF)-beta may play a role in the control of normal epithelial cell proliferation and differentiation. In addition, TGF-beta has a centra l role in extracellular matrix homeostasis and regulates the immune respons e at the local level. In this study immunohistochemistry was used to examin e the pattern of TGF-beta protein distribution and quantitative reverse tra nscription-polymerase chain reaction (RT-PCR) to determine levels of TGF-be ta messenger RNA expression in normal intestinal mucosa and in the flat muc osa of children with celiac disease. Methods: Small intestinal biopsies were performed in children with active c eliac disease and in histologically normal control subjects. Frozen section s were single stained using an anti-TGF-beta monoclonal antibody and were d ouble stained for TCF-beta and T cell, macrophages, and the activation mark er CD25. Total RNA was extracted from frozen specimens and competitive quan titative RT-PCR performed for TGF-beta mRNA using internal synthetic standa rd RNA. Results: In normal intestinal mucosa, by immunohistochemistry, TGF-beta exp ression was most prominent in the villous tip epithelium, whereas in the la mina propria, weak immunoreactivity was present. The celiac mucosa showed w eak and patchy epithelial TGF-beta immunoreactivity. In contrast, an intens e staining positivity was present in the lamina propria localized mostly in the subepithelial region where T cells, macrophages, and CD25(+) cells wer e detected by double staining. By quantitative RT-PCR, levels of TGF-beta m RNA transcripts appeared to be increased in celiac intestinal mucosa compar ed with chat: in control subjects, although the difference did not reach st atistical significance. Conclusions: These observations suggest that TGF-beta expression is associa ted with differentiated enterocyte function. In celiac disease the lower TG F-beta epithelial cell expression could be a consequence of the preponderan ce of a less differentiated epithelial cell phenotype also present in the s urface epithelium. In contrast, the prominent TGF-beta positivity of the su bepithelial lamina propria suggests an association with the local immune an d inflammatory response, as well as a potential role of these peptides in m esenchymal-epithelial cell interaction.