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Parenteral nutrition impairs lymphotoxin β receptor signaling via NF-κB

Jinggang Lan1, Aaron F Heneghan, Yoshifumi Sano

  • 1Surgical Service, William S. Middleton Memorial Veterans Hospital, Madison WI, USA.

Annals of Surgery
|March 4, 2011
PubMed
Abstract

Insights

Parenteral nutrition (PN) reduces NF-κB pathways in Peyer's patches (PP). Lymphotoxin β receptor (LTβR) stimulation during PN restores these pathways, while LTβR blockade reduces them, impacting immune cell trafficking.

Area of Science:

  • Immunology
  • Gastroenterology
  • Molecular Biology

Background:

  • Lymphotoxin (LT) signaling via Lymphotoxin β receptor (LTβR) activates the noncanonical NF-κB pathway in Peyer's patches (PP), influencing immune responses.
  • Parenteral nutrition (PN) is known to decrease LTβR expression, MAdCAM-1, and chemokines in PP, potentially impairing immune function compared to chow-fed conditions.
  • Canonical NF-κB pathway activation by inflammatory stimuli contrasts with the noncanonical pathway, highlighting distinct immune signaling mechanisms.

Purpose of the Study:

  • To investigate the impact of parenteral nutrition (PN) on NF-κB activation pathways in Peyer's patches (PP).
  • To evaluate the effects of exogenous Lymphotoxin β receptor (LTβR) stimulation and blockade on NF-κB pathways and associated molecules during PN or chow feeding.
  • To determine the influence of these interventions on MAdCAM-1, chemokines (CCL19, CCL20, CCL25), and cytokines (IL-4, IL-10) in PP.

Main Methods:

  • Animals were maintained on either chow or parenteral nutrition (PN) for 5 days.
  • Exogenous LTβR stimulation or blockade was administered for 2 or 3 days, respectively.
  • NF-κB proteins (canonical: p50/p65; noncanonical: p52/RelB) in PP were quantified using TransAM NF-κB kits, and MAdCAM-1, chemokines, and cytokines were measured by ELISA.

Main Results:

  • PN significantly reduced all analyzed NF-κB proteins in PP compared to chow.
  • LTβR stimulation during PN increased noncanonical NF-κB proteins (p52, RelB), MAdCAM-1, IL-4, and IL-10, but did not affect p65 or specific chemokines.
  • LTβR blockade in chow-fed animals decreased noncanonical NF-κB products, MAdCAM-1, chemokines, and cytokines, with no impact on the canonical pathway.

Conclusions:

  • Parenteral nutrition (PN) suppresses both canonical and noncanonical NF-κB pathways in Peyer's patches (PP) due to lack of enteral stimulation.
  • LTβR stimulation during PN effectively restores PP noncanonical NF-κB activity and associated molecules, partially restoring the canonical pathway.
  • LTβR blockade in PP reduces noncanonical NF-κB activity, MAdCAM-1, chemokines, and cytokines without affecting the canonical NF-κB pathway.

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