Document Detail


TNFα inhibitors restrict T cell activation and cycling via Notch-1 signalling in inflammatory bowel disease.
MedLine Citation:
PMID:  22068169     Owner:  NLM     Status:  Publisher    
Abstract/OtherAbstract:
BackgroundTumour necrosis factor α (TNFα) inhibitors such as adalimumab and infliximab are frequently prescribed for inflammatory bowel disease (IBD). Despite the clinical success of TNFα inhibitors, their physiological mode of action is not fully understood. The aim of this study was to investigate the mode of action of anti-TNFα agents in IBD.MethodsIt was hypothesised that Notch mediates anti-TNFα action in T cells. A study was carried out to identify Notch-1 as a link by which anti-TNFα antibodies mediate their inhibitory functions.ResultsTNFα inhibitors induced T cell apoptosis, inhibited activation, reduced cytokine secretion and restricted cell cycling. TNFα blockade at several levels showed that TNFα is responsible for inducing apoptosis by anti-TNFα but not for cell cycle restriction. By linking Notch and TNFα it was shown that (1) Notch-1 mucosal expression differs in inflamed and non-inflamed mucosa and increases in response to anti-TNFα treatment; (2) Notch-1 function is regulated by TNFα inhibitors; (3) Notch-1 binds to TNFα; and (4) Notch-1 inhibition prevents anti-TNFα-induced T cell cycle arrest but not apoptosis.ConclusionsTNFα inhibitors potently inhibit T cell function. By demonstrating for the first time that Notch-1 mediates the inhibitory effects of adalimumab and infliximab on T cell cycling, this study reveals a new mode of action and also an underlying signalling pathway by which biological agents act in IBD.
Authors:
Lael Werner; Uta Berndt; Daniela Paclik; Silvio Danese; Anja Schirbel; Andreas Sturm
Related Documents :
23988449 - Sigma 1 receptor plays a prominent role in il-24-induced cancer-specific apoptosis.
24418339 - Novel polysaccharide from radix cyathulae officinalis kuan can improve immune response...
24634219 - A novel small-molecule tnfα inhibitor attenuates inflammation in a hepatitis mouse model.
23321929 - Cyclooxygenase-2 generates the endogenous mutagen trans-4-hydroxy-2-nonenal in enteroco...
24037489 - Effects of psycho-behavioral interventions on immune functioning in cancer patients: a ...
23677569 - Oligonucleotide suppression of bcl-2 in lncap cells is compensated by increased androge...
5085239 - The effect of anti-inflammatory agents on the changes in local lymph after thermal injury.
16500719 - Effect of erythropoietin on staurosporine-induced apoptosis and differentiation of sh-s...
15240189 - Increased ability of peripheral blood lymphocytes to degrade laminin in multiple sclero...
Publication Detail:
Type:  JOURNAL ARTICLE     Date:  2011-11-7
Journal Detail:
Title:  Gut     Volume:  -     ISSN:  1468-3288     ISO Abbreviation:  -     Publication Date:  2011 Nov 
Date Detail:
Created Date:  2011-11-9     Completed Date:  -     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  2985108R     Medline TA:  Gut     Country:  -    
Other Details:
Languages:  ENG     Pagination:  -     Citation Subset:  -    
Affiliation:
Division of Gastroenterology and Hepatology, Charité Campus Virchow Clinic, Universitätsmedizin Berlin, Berlin, Germany.
Export Citation:
APA/MLA Format     Download EndNote     Download BibTex
MeSH Terms
Descriptor/Qualifier:

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


Previous Document:  Flt3 ligand expands CD103? dendritic cells and FoxP3? T regulatory cells, and attenuates Crohn's-lik...
Next Document:  Increased alveolar nitric oxide and systemic inflammation markers in silica-exposed workers.