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IL-4 Signaling Mechanisms in Inflammatory Bowel Disease Mononuclear Phagocytes.
MedLine Citation:
PMID:  23282589     Owner:  NLM     Status:  In-Data-Review    
Abstract/OtherAbstract:
: In inflammatory bowel disease (IBD), intestinal mononuclear cells secrete increased amounts of proinflammatory cytokines interleukin-1β (IL-1β), tumor necrosis factor-α (TNF-α), as well as nonspecific effector molecules (i.e., superoxide anions) in vitro and in vivo. Interleukin-4 (IL-4) is an important contrainflammatory cytokine to limit monocyte and macrophage activation. Data obtained with peripheral monocytes indicate that IL-4-mediated downregulation of activation may be impaired in IBD. High IL-4 concentrations are able to overcome the impairment in downregulation of proinflammatory cytokines and superoxide anions, respectively. We investigated molecular events involved in IL-4-induced signal transduction and regulation in IBD mononuclear phagocytes. Peripheral blood mononuclear cells were isolated by densitygradient centrifugation, intestinal lamina propria mononuclear cells by collagenase digestion. Proinflammatory cytokine mRNA levels were assessed by semiquantitative polymerase chain reaction using internal standards. IL-4 receptor expression was investigated by radiolabeled ligand binding studies and IL-4 receptor signal transduction by specific induction of signal transducer and activator of transcription 6 (Stat 6). Downregulation of TNF-α and IL-1β mRNA levels, respectively, in IBD mononuclear phagocytes is impaired in comparison with normal cells. However, no differences between IBD and normal control mononuclear phagocytes were seen in IL-4 receptor surface expression and signal transduction by IL-4induced generation of Stat 6. Impaired downregulation of TNF-α and IL-1β secretion by IL-4 in IBD mononuclear phagocytes is also seen on the mRNA level. The mechanism of IL-4 resistance may be located in elements of IL-4 receptor signal transduction downstream of Stat 6.
Authors:
Y Rückert; U Schindler; T Heinig; S Nikolaus; A Raedler; S Schreiber
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Publication Detail:
Type:  Journal Article    
Journal Detail:
Title:  Inflammatory bowel diseases     Volume:  2     ISSN:  1078-0998     ISO Abbreviation:  Inflamm. Bowel Dis.     Publication Date:  1996  
Date Detail:
Created Date:  2013-01-03     Completed Date:  -     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  9508162     Medline TA:  Inflamm Bowel Dis     Country:  United States    
Other Details:
Languages:  eng     Pagination:  244-52     Citation Subset:  -    
Affiliation:
Humboldt University, Charité, *IVth Department of Medicine (Gastroenterology), and †Outpatient Clinics of Internal Medicine, Berlin, Germany; ‡Tularic Inc., San Francisco, California, U.S.A.; and §Tabea, Inflammatory Bowel Disease Center, Hamburg, Germany.
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