Transforming growth factor-β messenger RNA and protein in murine colitis

Abstract

Using a CD4+ T-cell-transplanted SCID mouse model of colitis, we have analyzed TGF-β transcription and translation in advanced disease. By in situ hybridization, the epithelium of both control and inflamed tissues transcribed TGF-β1 and TGF-β3 mRNAs, but both were expressed significantly farther along the crypt axis in disease. Control lamina propria cells transcribed little TGF-β1 or TGF-β3 mRNA, but in inflamed tissues many cells expressed mRNA for both isoforms. No TGF-β2 message was detected in either control or inflamed tissues. Immunohistochemistry for latent and active TGF-β1 showed that all cells produced perinuclear latent TGF-β1. The epithelial cell basal latent protein resulted in only low levels of subepithelial active protein, which co-localized with collagen IV and laminin in diseased and control tissue. Infiltrating cells expressed very Iow levels of active TGF-β. By ELISA, very low levels (0-69 pg/mg) of soluble total or active TGF-β were detected in hypotonic tissue lysates. TGF-β1 and TGF-β3 are produced by SCID mouse colon and transcription is increased in the colitis caused by transplantation of CD4+ T-cells, but this does not result in high levels of soluble active protein. Low levels of active TGF-β may be a factor contributing to unresolved inflammation.