Literature DB >> 21368655

Parenteral nutrition impairs lymphotoxin β receptor signaling via NF-κB.

Jinggang Lan1, Aaron F Heneghan, Yoshifumi Sano, Mark A Jonker, Jiro Omata, Wentong Xu, Joseph F Pierre, Kenneth A Kudsk.   

Abstract

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.

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Year:  2011        PMID: 21368655      PMCID: PMC3079800          DOI: 10.1097/SLA.0b013e31821224eb

Source DB:  PubMed          Journal:  Ann Surg        ISSN: 0003-4932            Impact factor:   12.969


  29 in total

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