Advanced age exacerbates intestinal epithelial permeability after burn injury in mice.

Abstract

BACKGROUND:

Advanced age is an independent risk factor for morbidity and mortality after burn injury. Following burn, the intestines can become permeable leading to the leakage of bacteria and their products from the lumen of the ileum to the portal and systemic circulation. Here, we sought to determine the effects of advanced age on intestinal permeability post burn injury and assess intestinal inflammatory biomarkers.

METHODS:

Young (4-5 months) and aged (18-22 months) female BALB/cBy mice were subjected to a 12-15% total body surface area (TBSA) sham or burn injury. 24 h after injury, mice were euthanized, and organs collected. Colony-forming units (CFU) were counted from plated mesenteric lymph nodes (MLN). Gene expression of ileal tight junctional proteins, occludin and zonula occludens 1 (ZO-1), in addition to ileal damage associated molecular pattern (DAMP) proteins, S100A8 and S100A9, as well as ileal inflammatory markers IL-6 and TNF-α were measured by qPCR. Intestinal cell death was measured by ELISA. Intestinal permeability was determined by FITC fluorescence in serum; 4kD FITC-dextran was given by oral gavage 3 h before euthanasia.

RESULTS:

Aged mice subjected to burn injury had increased intestinal permeability as evidenced by a 5.8-fold higher level of FITC-dextran in their serum when compared to all other groups (p < 0.05). In addition, aged burn-injured mice exhibited heightened bacterial accumulation in the MLN with a 15.5-fold increase over all other groups (p < 0.05). Histology of ileum failed to show differences in villus length among all groups. Analysis of ileal tight junctional proteins and inflammatory marker gene expression revealed no difference in Ocln, Tjp1, Il6, or Tnf expression among all groups, but 2.3 and 2.9-fold upregulation of S100a8 and S100a9, respectively, in aged burn-injured mice relative to both young groups and aged sham-injured mice (p < 0.05). Lastly, cell death in the ileum was elevated more than two-fold in aged burn-injured mice relative to young animals regardless of injury (p < 0.05).

CONCLUSIONS:

These data demonstrate that advanced age exacerbates intestinal epithelial permeability after burn injury. Heightened apoptosis may be responsible for the elevated intestinal leakiness and accumulation of bacteria in mesenteric lymph nodes. In addition, S100a8/9 may serve as a biomarker of elevated inflammation within the intestine.

• Authors: Kevin M Najarro, Devin M Boe, Travis M Walrath, Juliet E Mullen, Madison T Paul, John H Frankel, Holly J Hulsebus, Juan-Pablo Idrovo, Rachel H McMahan, Elizabeth J Kovacs
• Journal: Experimental gerontology (Exp Gerontol) Vol. 158 Pg. 111654 (02 2022) ISSN: 1873-6815 [Electronic] England
• PMID: 34915110 (Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, U.S. Gov't, Non-P.H.S.)
• Copyright: Copyright © 2021. Published by Elsevier Inc.

Chemical References

• Occludin

Topics

• Animals
• Female
• Intestinal Mucosa (metabolism)
• Intestines
• Mice
• Occludin (metabolism, pharmacology)
• Permeability
• Tight Junctions (metabolism)