Transforming growth factor-β1 protects against intestinal epithelial barrier dysfunction caused by hypoxia-reoxygenation

Kathryn L. Howe, Robert J. Lorentz, Amit Assa, Lee J. Pinnell, Kathene C. Johnson-Henry, Philip M. Sherman

Research output: Contribution to journalArticlepeer-review

9 Scopus citations


Intestinal epithelia regulate barrier integrity when challenged by inflammation, oxidative stress, and microbes. Transforming growth factor-β1 (TGF-β1) is a cytokine with known beneficial effects on intestinal epithelia, including barrier enhancement, after exposure to proinflammatory cytokines and infectious agents. The aim of this study was to determine whether TGF-β1 directly protects intestinal epithelia during hypoxia-reoxygenation (HR). Intestinal epithelial monolayers (T84, Caco-2bbe) were exposed to either hypoxia (1% O2, 1 h) or oxidative stress (hydrogen peroxide, 1 mM), followed by normoxic atmosphere for different time points in the absence and presence of varying concentrations of TGF-β1. Transepithelial electrical resistance (TER) assessed barrier function, with RNA extracted for reverse transcription polymerase chain reaction analysis of GPx-1, HIF-1, heme-oxygenase-1 (HO-1), and NOX-1. In some experiments, intestinal epithelia were exposed to enterohemorrhagic Escherichia coli (EHEC) O157:H7 during the reoxygenation period and TER recorded 7 h after the infectious challenge. Hypoxia-reoxygenation significantly decreased TER in intestinal epithelia compared with normoxic controls. Transforming growth factor-β1 pretreatment ameliorated HR-induced epithelial barrier dysfunction in T84 (at 1 Y 3 h) and Caco-2bbe (1 h) monolayers. Transforming growth factor-β1 preserved barrier integrity for up to 16 h after challenge with hydrogen peroxide. In TGF-β1Ytreated epithelial monolayers, only HO-1 mRNA significantly increased after HR (P G 0.05 vs. normoxic controls). The EHEC-induced epithelial barrier dysfunction was significantly worsened by intestinal HR (P G 0.05 vs. normoxia-EHECYinfected cells), but this was not protected by TGF-β1 pretreatment. Transforming growth factor-β1 preserves loss of epithelial barrier integrity caused by the stress of HR via a mechanism that may involve the upregulation of HO-1 transcription. Targeted treatment with TGF-" could lead to novel therapies in enteric diseases characterized by HR injury.

Original languageEnglish
Pages (from-to)483-489
Number of pages7
Issue number5
StatePublished - 21 May 2015
Externally publishedYes


  • Ischemia-reperfusion
  • antioxidant
  • cytokine
  • intestinal permeability

ASJC Scopus subject areas

  • Emergency Medicine
  • Critical Care and Intensive Care Medicine


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