Stress ulcers are a common complication in critically ill patients, but the underlying mechanism is little known. This study characterized the function of the p50 subunit of NF-kappa B in an experimental model of cold immobilization stress-induced gastric ulcers. Stress-induced gastric mucosal inflammation and gastric injury were examined in wild-type and NF-kappa B p50-deficient mice. When subjected to cold immobilization stress, NF-kappa B was rapidly activated in the gastric mucosa in WT mice whereas the majority of kappa B DNA-binding activity was abrogated from p50(-/-) mice. Deficiency of p50 ameliorated stress-induced expression of TNF-alpha, MIP-2, and ICAM-1, resulting in reduced mucosal accumulation of neutrophils and gastric injury. These data indicated a critical role for the p50 in the gastric mucosal inflammatory response to cold restraint stress. (C) 2013 Elsevier Inc. All rights reserved.