Transforming growth factor-beta messenger RNA and protein in murine colitis.
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.
Whiting
C V
CV
Department of Clinical Veterinary Science, University of Bristol, Bristol, United Kingdom. c.v.whiting@bris.ac.uk
Williams
A M
AM
Claesson
M H
MH
Bregenholt
S
S
Reimann
J
J
Bland
P W
PW
D000818:Animals; D015496:CD4-Positive T-Lymphocytes / Q000637:transplantation; D003092:Colitis / Q000209:etiology / Q000235:genetics / Q000276:immunology* / Q000473:pathology; D003106:Colon / Q000473:pathology; D003238:Connective Tissue / Q000473:pathology; D004797:Enzyme-Linked Immunosorbent Assay; D019084:Fluorescent Antibody Technique, Indirect; D007150:Immunohistochemistry; D017403:In Situ Hybridization; D015212:Inflammatory Bowel Diseases / Q000209:etiology / Q000235:genetics / Q000276:immunology* / Q000473:pathology; D051379:Mice; D016513:Mice, SCID; D012333:RNA, Messenger / Q000302:isolation & purification; D014018:Tissue Distribution; D016212:Transforming Growth Factor beta / Q000096:biosynthesis* / Q000235:genetics
D012333:RNA, Messenger; D016212:Transforming Growth Factor beta