Tumour Necrosis Factor-alpha (TNF-alpha) Transcription and Translation in the CD4+ T Cell-transplanted Scid Mouse Model of Colitis

Overview

Journal Clin Exp Immunol

Publisher Oxford University Press

Specialty Allergy & Immunology

Date 1999 Jun 11

PMID 10361228

Citations 5

Authors

A M Williams

C V Whiting

K Bonhagen

J Reimann

S Bregenholt

M H Claesson

P W Bland

Affiliations

Soon will be listed here.

Abstract

The adoptive transfer of activated CD4+ alpha/beta T cell blasts from the spleens of immunocompetent C.B-17+/+ or BALB/cdm2 mice into C.B-17scid/scid (scid) mice induces a colitis in the scid recipient within 8 weeks, which progresses to severe disease within 16 weeks. T cells isolated from recipient colon show a Th1 cytokine phenotype. We have examined the relationship between the phenotype of the cellular infiltrate and the transcription and translation of the proinflammatory cytokine TNF-alpha. The techniques of double indirect immunohistology and in situ hybridization using digoxigenin-labelled riboprobes were used. The prominent myeloid cell infiltrate in diseased tissues comprised F4/80+, Mac-l+ macrophages, neutrophils, dendritic cells and activated macrophages. TNF-alpha transcription and translation were associated with activated macrophages in the lamina propria. Activated macrophages transcribing and translating TNF-alpha were clustered in areas of tissue destruction. Crypt epithelium of inflamed tissues transcribed TNF-alpha at a very early stage of the disease process, but translation of TNF-alpha protein could only be found in advanced epithelial dysplasia. This indicates differential post-transcriptional control of TNF-alpha in activated macrophages and the epithelium.

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