Using a CD4(+) T-cell-transplanted SCID mouse model of colitis, we have ana
lyzed TGF-beta transcription and translation in advanced disease. By in sit
u hybridization, the epithelium of both control and inflamed tissues transc
ribed TGF-beta1 and TGF-beta3 mRNAs, but both were expressed significantly
farther along the crypt axis in disease. Control lamina propria cells trans
cribed little TGF-beta1 or TGF-beta3 mRNA, but in inflamed tissues many cel
ls expressed mRNA for both isoforms. No TGF-beta2 message was detected in e
ither control or inflamed tissues. Immunohistochemistry for latent and acti
ve TGF-beta1 showed that all cells produced perinuclear latent TGF-beta1. T
he epithelial cell basal latent protein resulted in only low levels of sube
pithelial active protein, which co-localized with collagen IV and laminin i
n diseased and control tissue. Infiltrating cells expressed very low levels
of active TGF-beta. By ELISA, very low levels (0-69 pg/mg) of soluble tota
l or active TGF-beta were detected in hypotonic tissue lysates. TGF-beta1 a
nd TGF-beta3 are produced by SCID mouse colon and transcription is increase
d in the colitis caused by transplantation of CD4+ T-cells, but this does n
ot result in high levels of soluble active protein. Low levels of active TG
F-beta may be a factor contributing to unresolved inflammation.