Document Detail


Parenteral nutrition impairs lymphotoxin β receptor signaling via NF-κB.
MedLine Citation:
PMID:  21368655     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
OBJECTIVE: To determine effects of (1) parenteral nutrition (PN), (2) exogenous Lymphotoxin β receptor (LTβR) stimulation in PN animals, and (3) exogenous LTβR blockade in chow animals on NF-κB activation pathways and products: MAdCAM-1, chemokine (C-C motif) Ligand (CCL) 19, CCL20, CCL25, interleukin (IL)-4, and IL-10.
BACKGROUND: LT stimulates LTβR in Peyer's patches (PP) to activate NF-κB via the noncanonical pathway. The p100/RelB precursor yields p52/RelB producing MAdCAM-1, cytokines, and chemokines important in cell trafficking. TNFα, IL-1β, and bacterial products stimulate the inflammatory canonical NF-κB pathway producing p65/p50 and c-Rel/p50. PN decreases LTβR, MAdCAM-1, and chemokines in PP and lowers small intestinal IgA compared with chow.
METHODS: Canonical (p50 and p65) and noncanonical (p52 and Rel B) NF-κB proteins in PP were analyzed by TransAM NF-κB kit after 5 days of chow or PN, 2 days of LTβR stimulation or 3 days of LTβR blockade. MAdCAM-1, chemokines, and cytokines in PP were measured by ELISA after LTβR stimulation or blockade.
RESULTS: PN significantly reduced all NF-κB proteins in PP compared with chow. Exogenous LTβR stimulation during PN increased p50, p52, Rel B, MAdCAM-1, IL-4, and IL-10 in PP, but not p65, CCL19, CCL20, or CCL25 compared with PN. LTβR blockade reduced noncanonical products (p52 and Rel B), MAdCAM-1, CCL19, CCL20, CCL25, IL-4, and IL-10 but had no effect on the inflammatory pathway (p50 and p65) compared with chow.
CONCLUSION: Lack of enteral stimulation during PN decreases both canonical and noncanonical NF-κB pathways in PP. LTβR stimulation during PN feeding completely restores PP noncanonical NF-κB activity, MAdCAM-1, IL-4, IL-10, and partly the canonical pathway. LTβR blockade decreases the noncanonical NF-κB activity, MAdCAM-1, chemokines, and cytokines without effect on the canonical NF-κB activity in PP.
Authors:
Jinggang Lan; Aaron F Heneghan; Yoshifumi Sano; Mark A Jonker; Jiro Omata; Wentong Xu; Joseph F Pierre; Kenneth A Kudsk
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Publication Detail:
Type:  Comparative Study; Journal Article; Research Support, N.I.H., Extramural; Research Support, U.S. Gov't, Non-P.H.S.    
Journal Detail:
Title:  Annals of surgery     Volume:  253     ISSN:  1528-1140     ISO Abbreviation:  Ann. Surg.     Publication Date:  2011 May 
Date Detail:
Created Date:  2011-04-19     Completed Date:  2011-06-23     Revised Date:  2012-05-02    
Medline Journal Info:
Nlm Unique ID:  0372354     Medline TA:  Ann Surg     Country:  United States    
Other Details:
Languages:  eng     Pagination:  996-1003     Citation Subset:  AIM; IM    
Affiliation:
Surgical Service, William S. Middleton Memorial Veterans Hospital, Madison WI, USA.
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MeSH Terms
Descriptor/Qualifier:
Analysis of Variance
Animals
Chemokines / metabolism
Cytokines / metabolism
Disease Models, Animal
Immunoglobulins / metabolism
Interleukin-10 / metabolism
Interleukin-4 / metabolism
Intestinal Mucosa / metabolism
Lymphotoxin beta Receptor / metabolism*,  physiology
Male
Mice
Mice, Inbred Strains
Mucoproteins / metabolism
NF-kappa B / metabolism*
Parenteral Nutrition / adverse effects*,  methods
Random Allocation
Sensitivity and Specificity
Signal Transduction*
Grant Support
ID/Acronym/Agency:
R01 GM053439-13/GM/NIGMS NIH HHS; R01 GM53439/GM/NIGMS NIH HHS
Chemical
Reg. No./Substance:
0/Chemokines; 0/Cytokines; 0/Immunoglobulins; 0/Lymphotoxin beta Receptor; 0/MADCAM1 protein, human; 0/Mucoproteins; 0/NF-kappa B; 130068-27-8/Interleukin-10; 207137-56-2/Interleukin-4

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