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Nuclear Factor–B Is Activated in Intestinal Mucosa During Endotoxemia

Timothy A. Pritts, MD; M. Ryan Moon, MD; Josef E. Fischer, MD; Andrew L. Salzman, MD; Per-Olof Hasselgren, MD

Arch Surg. 1998;133:1311-1315.

Background  The transcription factor nuclear factor–B (NF-B) regulates a large number of genes involved in the inflammatory response to critical illness. The intestinal mucosa plays an active role in the inflammatory and metabolic response to sepsis and endotoxemia, but it is not known if NF-B is activated in the mucosa during these conditions.

Objective  To test the hypothesis that endotoxemia in mice activates NF-B in intestinal mucosa.

Methods  Mice were injected subcutaneously with lipopolysaccharide, 12.5 mg/kg, or a corresponding volume of saline. At various intervals following injection, jejunal mucosa was harvested and nuclear and cytoplasmic fractions were prepared. The nuclear fractions were analyzed by electrophoretic mobility shift assay for NF-B activation and by Western blot analysis for the NF-B subunits p50 and p65. Cytoplasmic fractions were analyzed by Western blotting for the NF-B inhibitory proteins IB- and IB-.

Results  Electrophoretic mobility shift assay showed that NF-B was activated in jejunal mucosa 1 hour after injection of lipopolysaccharide and persisted for at least 4 hours. The NF-B subunits p50 and p65 were present in nuclear fractions of mucosa from endotoxemic mice at the corresponding time points. Cytoplasmic levels of the inhibitory proteins IB- and IB- decreased during endotoxemia, and the proteins were nearly absent 60 minutes after injection of lipopolysaccharide.

Conclusions  The results suggest that IB is degraded and NF-B is activated in intestinal mucosa during endotoxemia. The findings support the concept that the intestinal mucosa is an important component of the inflammatory response to sepsis and endotoxemia.

From the Department of Surgery, University of Cincinnati (Drs Pritts, Moon, Fischer, and Hasselgren); Division of Critical Care, Children's Hospital Medical Center (Dr Salzman); and Shriners Hospital for Children (Drs Pritts, Moon, Fischer, and Hasselgren), Cincinnati, Ohio.

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