Document Detail


Interleukin-15 receptor α expression in inflammatory bowel disease patients before and after normalization of inflammation with infliximab.
MedLine Citation:
PMID:  23039249     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
Interleukin-15 (IL-15) is a pro-inflammatory cytokine thought to contribute to the inflammation in inflammatory bowel diseases (IBD). The specific receptor chain IL-15Rα can be expressed as a transmembranous signalling receptor, or can be cleaved by a disintegrin and metalloprotease domain 17 (ADAM17) into a neutralizing, soluble receptor (sIL-15Rα). The aim of this study is to evaluate the expression of IL-15Rα in ulcerative colitis (UC) and Crohn's disease (CD) patients before and after infliximab (IFX) therapy. Gene expression of IL-15Rα, IL-15 and ADAM17 was measured at the mRNA level by quantitative reverse transcription-PCR in mucosal biopsies harvested before and after first IFX therapy. Concentrations of sIL-15Rα were measured in sera of patients by ELISA and IL-15Rα protein was localized in the gut by immunohistochemistry and immunofluorescence. Mucosal expression of IL-15Rα is increased in UC and CD patients compared with controls and it remains elevated after IFX therapy in both responder and non-responder patients. The concentration of sIL-15Rα in serum is also increased in UC patients when compared with controls and does not differ between responders and non-responders either before or after IFX. CD patients have levels of sIL-15Rα comparable to healthy controls before and after therapy. In mucosal tissues, IL-15Rα(+) cells closely resemble activated memory B cells with a pre-plasmablastic phenotype. To conclude, IBD patients have an increased expression of IL-15Rα mRNA in the mucosa. Expression is localized in B cells, suggesting that IL-15 regulates B-cell functions during bowel inflammation. No change in release of sIL-15Rα is observed in patients treated with IFX.
Authors:
Clémentine Perrier; Ingrid Arijs; Dominiek Staelens; Christine Breynaert; Isabelle Cleynen; Kris Covens; Marc Ferrante; Gert Van Assche; Séverine Vermeire; Gert de Hertogh; Frans Schuit; Paul Rutgeerts; Jan L Ceuppens
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  Immunology     Volume:  138     ISSN:  1365-2567     ISO Abbreviation:  Immunology     Publication Date:  2013 Jan 
Date Detail:
Created Date:  2012-12-17     Completed Date:  2013-03-27     Revised Date:  2013-04-16    
Medline Journal Info:
Nlm Unique ID:  0374672     Medline TA:  Immunology     Country:  England    
Other Details:
Languages:  eng     Pagination:  47-56     Citation Subset:  IM    
Copyright Information:
© 2012 Blackwell Publishing Ltd.
Affiliation:
Department of Gastroenterology, Translational Research Centre for Gastrointestinal Disorders (TARGID), KU Leuven, Leuven, Belgium. Clementine.Perrier@med.kuleuven.be
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MeSH Terms
Descriptor/Qualifier:
Adult
Anti-Inflammatory Agents, Non-Steroidal / pharmacology*,  therapeutic use
Antibodies, Monoclonal / pharmacology*,  therapeutic use*
Colitis, Ulcerative / drug therapy*,  immunology
Crohn Disease / drug therapy*,  immunology
Enzyme-Linked Immunosorbent Assay
Female
Fluorescent Antibody Technique
Humans
Immunohistochemistry
Inflammation / drug therapy
Interleukin-15 Receptor alpha Subunit / biosynthesis*,  genetics,  immunology*
Male
Middle Aged
RNA, Messenger / genetics
Reverse Transcriptase Polymerase Chain Reaction
Young Adult
Chemical
Reg. No./Substance:
0/Anti-Inflammatory Agents, Non-Steroidal; 0/Antibodies, Monoclonal; 0/Interleukin-15 Receptor alpha Subunit; 0/RNA, Messenger; 0/infliximab

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