Burn-induced gut barrier injury is attenuated by phosphodiesterase inhibition: Effects on tight junction structural proteins

Todd W. Costantini, William H. Loomis, James G. Putnam, Dana Drusinsky, Jessica Deree, Sung Hyuk Choi, Paul Wolf, Andrew Baird, Brian Eliceiri, Vishal Bansal, Raul Coimbra

Research output: Contribution to journalArticle

71 Citations (Scopus)

Abstract

Loss of intestinal barrier function after burn injury allows movement of intraluminal contents across the mucosa, which can lead to the development of distant organ injury and multiple organ failure. Tight junction function is highly regulated by membrane-associated proteins including occludin and zonula occludens protein 1 (ZO-1), which can be modulated by systemic inflammation. We hypothesized that (1) burn injury leads to gut barrier injury, and (2) phosphodiesterase inhibition will attenuate these burn-induced changes. Male balb/c mice undergoing a 30% steam burn were randomized to resuscitation with normal saline or normal saline + pentoxifylline (PTX; 12.5 mg/kg). Intestinal injury was assessed by histological diagnosis and TNF-a levels using enzyme-linked immunosorbent assay. Intestinal permeability was assessed by measuring the plasma concentration of fluorescein isothiocyanate-dextran after intraluminal injection in the distal ileum. Occludin and ZO-1 levels were analyzed by immunoblotting and immunohistochemistry. Thirty percent total body surface area (TBSA) burn results in a significant increase in intestinal permeability. Treatment with PTX after burn attenuates intestinal permeability to sham levels. Burn injury resulted in a marked decrease in the levels of tight junction proteins occludin and ZO-1 at 6 and 24 h. The use of PTX after burn significantly decreases the breakdown of occludin and ZO-1. Pentoxifylline also attenuates the burn-induced increase in plasma and intestinal TNF-α. Confocal microscopy demonstrates that PTX attenuates the burn-induced reorganization of occludin and ZO-1 away from the tight junction. Pentoxifylline attenuates burn-induced intestinal permeability and decreases the breakdown and reorganization of intestinal occludin and ZO-1. Therefore, phosphodiesterase inhibition may be a useful adjunct strategy in the attenuation of bum-induced gut barrier injury.

Original languageEnglish
Pages (from-to)416-422
Number of pages7
JournalShock
Volume31
Issue number4
DOIs
Publication statusPublished - 2009 Apr 1
Externally publishedYes

Fingerprint

Tight Junction Proteins
Zonula Occludens-1 Protein
Occludin
Phosphoric Diester Hydrolases
Burns
Wounds and Injuries
Pentoxifylline
Permeability
Tight Junctions
Multiple Organ Failure
Body Surface Area
Steam
Ileum
Immunoblotting
Confocal Microscopy
Resuscitation
Membrane Proteins
Mucous Membrane
Enzyme-Linked Immunosorbent Assay
Immunohistochemistry

Keywords

  • Confocal microscopy
  • Histological injury
  • Intestinal permeability
  • Occludin
  • Pentoxifylline
  • Shock
  • TNF-α
  • ZO-1

ASJC Scopus subject areas

  • Emergency Medicine
  • Critical Care and Intensive Care Medicine

Cite this

Burn-induced gut barrier injury is attenuated by phosphodiesterase inhibition : Effects on tight junction structural proteins. / Costantini, Todd W.; Loomis, William H.; Putnam, James G.; Drusinsky, Dana; Deree, Jessica; Choi, Sung Hyuk; Wolf, Paul; Baird, Andrew; Eliceiri, Brian; Bansal, Vishal; Coimbra, Raul.

In: Shock, Vol. 31, No. 4, 01.04.2009, p. 416-422.

Research output: Contribution to journalArticle

Costantini, TW, Loomis, WH, Putnam, JG, Drusinsky, D, Deree, J, Choi, SH, Wolf, P, Baird, A, Eliceiri, B, Bansal, V & Coimbra, R 2009, 'Burn-induced gut barrier injury is attenuated by phosphodiesterase inhibition: Effects on tight junction structural proteins', Shock, vol. 31, no. 4, pp. 416-422. https://doi.org/10.1097/SHK.0b013e3181863080
Costantini, Todd W. ; Loomis, William H. ; Putnam, James G. ; Drusinsky, Dana ; Deree, Jessica ; Choi, Sung Hyuk ; Wolf, Paul ; Baird, Andrew ; Eliceiri, Brian ; Bansal, Vishal ; Coimbra, Raul. / Burn-induced gut barrier injury is attenuated by phosphodiesterase inhibition : Effects on tight junction structural proteins. In: Shock. 2009 ; Vol. 31, No. 4. pp. 416-422.
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