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

Citation
Cv. Whiting et al., Transforming growth factor-beta messenger RNA and protein in murine colitis, J HIST CYTO, 49(6), 2001, pp. 727-738
Citations number
43
Categorie Soggetti
Medical Research Diagnosis & Treatment
Journal title
JOURNAL OF HISTOCHEMISTRY & CYTOCHEMISTRY
ISSN journal
00221554 → ACNP
Volume
49
Issue
6
Year of publication
2001
Pages
727 - 738
Database
ISI
SICI code
0022-1554(200106)49:6<727:TGFMRA>2.0.ZU;2-4
Abstract
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.