Abstract
Using a CD4+ T-cell-transplanted SCID mouse model of colitis, we have analyzed TGF-beta transcription and translation in advanced disease. By in situ hybridization, the epithelium of both control and inflamed tissues transcribed TGF-beta1 and TGF-beta3 mRNAs, but both were expressed significantly farther along the crypt axis in disease. Control lamina propria cells transcribed little TGF-beta1 or TGF-beta3 mRNA, but in inflamed tissues many cells expressed mRNA for both isoforms. No TGF-beta2 message was detected in either control or inflamed tissues. Immunohistochemistry for latent and active TGF-beta1 showed that all cells produced perinuclear latent TGF-beta1. 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 low levels of active TGF-beta. By ELISA, very low levels (0-69 pg/mg) of soluble total or active TGF-beta were detected in hypotonic tissue lysates. TGF-beta1 and TGF-beta3 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-beta may be a factor contributing to unresolved inflammation.
| Original language | English |
|---|---|
| Journal | Journal of Histochemistry and Cytochemistry |
| Volume | 49 |
| Issue number | 6 |
| Pages (from-to) | 727-738 |
| Number of pages | 12 |
| ISSN | 0022-1554 |
| Publication status | Published - 1 Jun 2001 |
Keywords
- Animals
- CD4-Positive T-Lymphocytes
- Colitis
- Colon
- Connective Tissue
- Enzyme-Linked Immunosorbent Assay
- Fluorescent Antibody Technique, Indirect
- Immunohistochemistry
- In Situ Hybridization
- Inflammatory Bowel Diseases
- Mice
- Mice, SCID
- RNA, Messenger
- Tissue Distribution
- Transforming Growth Factor beta