Parenteral Nutrition Impairs Lymphotoxin β Receptor Signaling via NF-κB

Objective: To determine effects of (1) parenteral nutrition (PN), (2) exogenous Lymphotoxin beta receptor (LT beta R) stimulation in PN animals, and (3) exogenous LT beta R blockade in chow animals on NF-kappa B activation pathways and products: MAdCAM-1, chemokine (C-C motif) Ligand (CCL) 19, CCL20, CCL25, interleukin (IL)-4, and IL-10. Background: LT stimulates LT beta R in Peyer's patches (PP) to activate NF-kappa B via the noncanonical pathway. The p100/RelB precursor yields p52/RelB producingMAdCAM-1, cytokines, and chemokines important in cell trafficking. TNF alpha, IL-1 beta, and bacterial products stimulate the inflammatory canonical NF-kappa B pathway producing p65/p50 and c-Rel/p50. PN decreases LT beta R, 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-kappa B proteins in PP were analyzed by TransAM NF-kappa B kit after 5 days of chow or PN, 2 days of LT beta R stimulation or 3 days of LT beta R blockade. MAdCAM-1, chemokines, and cytokines in PP were measured by ELISA after LT beta R stimulation or blockade. Results: PN significantly reduced all NF-kappa B proteins in PP compared with chow. Exogenous LT beta R 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. LT beta R 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-kappa B pathways in PP. LT beta R stimulation during PN feeding completely restores PP noncanonical NF-kappa B activity, MAdCAM-1, IL-4, IL-10, and partly the canonical pathway. LT beta R blockade decreases the noncanonical NF-kappa B activity, MAdCAM-1, chemokines, and cytokines without effect on the canonical LT beta R activity in PP.