Abstract：
:The lymphotoxin-beta receptor (LTbetaR) pathway is critical for maintenance of organized lymphoid structures and is involved in the development of colitis. To investigate the mechanisms by which LTbetaR activation contributes to the pathology of chronic inflammation we used a soluble LTbetaR-Ig fusion protein as a competitive inhibitor of LTbetaR activation in the mouse model of chronic colitis induced by oral administration of dextran sulphate sodium. Strong expression of LTbeta which constitutes part of the LTalpha(1)beta(2) ligand complex was detected in colonic tissue of mice with chronic colitis. Treatment with LTbetaR-Ig significantly attenuated the development and histological manifestations of the chronic inflammation and reduced the production of inflammatory cytokines such as TNF, IL-1beta, and IL-6. Moreover, LTbetaR-Ig treatment significantly down-regulated mucosal addressin cell adhesion molecule-1 (MAdCAM-1) expression, leading to reduced leucocyte rolling and sticking in postcapillary and collecting venules and reduced extravasation into the intestinal mucosa as quantified by in vivo fluorescence microscopy. Thus, LTbetaR pathway inhibition ameliorates DSS-induced experimental chronic colitis in mice by MAdCAM-1 down-regulation entailing reduced lymphocyte margination and extravasation into the inflamed mucosa. Therefore, a combined treatment with reagents blocking T cell-mediated perpetuation of chronic inflammation such as LTbetaR-Ig together with direct anti-inflammatory reagents such as TNF inhibitors could constitute a promising treatment strategy for chronic colitis.
journal_name
Clin Exp Immunoljournal_title
Clinical and experimental immunologyauthors
Stopfer P,Obermeier F,Dunger N,Falk W,Farkas S,Janotta M,Möller A,Männel DN,Hehlgans Tdoi
10.1111/j.1365-2249.2004.02402.xsubject
Has Abstractpub_date
2004-04-01 00:00:00pages
21-9issue
1eissn
0009-9104issn
1365-2249pii
CEI2402journal_volume
136pub_type
杂志文章abstract：:With the aim of evaluating cell changes possibly induced by labelling lymphocytes with 99m-technetium (99mTc), several rosette tests and stimulation assays with mitogens have been carried out before and after radiolabelling. The results presented here show that (i) as the rosette tests are not modified statistically, ...
journal_title：Clinical and experimental immunology
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journal_title：Clinical and experimental immunology
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doi：
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journal_title：Clinical and experimental immunology
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doi：
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doi：
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doi：
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doi：
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journal_title：Clinical and experimental immunology
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