title: Interleukin-13 protects mouse intestine from ischemia and reperfusion injury through regulation of innate and adaptive immunity.
abstract: BACKGROUND
  Ischemia-reperfusion (I/R) injury is a major factor leading to intestinal dysfunction or graft loss after intestinal surgery or transplantation. This study investigated the cytoprotective effects and putative mechanisms of interleukin (IL)-13 after intestinal I/R injury in the mouse.
  
  
  METHODS
  Mouse warm intestinal I/R injury induced by clamping the superior mesenteric artery for 100 min with tissue analysis at 4 and 24 hr after reperfusion. Treated animals received intravenous recombinant murine IL-13 (rIL-13) and anti-IL-13 antibody, whereas controls received saline.
  
  
  RESULTS
  rIL-13 administration markedly prolonged animal survival (100% vs. 50% in saline controls) and resulted in near normal histopathological architecture. rIL-13 treatment also significantly decreased myeloperoxidase activity. Mice conditioned with rIL-13 had a markedly depressed Toll-like receptor-4 expression and increased the expression of Stat6, antioxidant hemeoxygenase-1, and antiapoptotic A20, Bcl-2/Bcl-xl, compared with that of controls. Unlike in controls, the expression of mRNA coding for IL-2/interferon-γ, and interferon-γ-inducible protein (IP)-10/monocyte chemotactic protein-1 remained depressed, whereas that of IL-13/IL-4 reciprocally increased in the mice treated with rIL-13. Administration of anti-IL13 antibody alone or in combination with rIL-13 resulted in outcomes similar to that seen in controls.
  
  
  CONCLUSIONS
  This study demonstrates for the first time that IL-13 plays a protective role in intestinal warm I/R injury and a critical role in the regulation of Stat6 and Toll-like receptor-4 signaling. The administration of IL-13 exerts cytoprotective effects in this model by regulating innate and adaptive immunity while the removal of IL-13 using antibody therapy abrogates this effect.
authors.affiliation: Division of Liver and Pancreas Transplantation, Department of Surgery, The Dumont-UCLA Transplant Center, David Geffen School of Medicine at UCLA, Los Angeles, CA, USA. dgfarmer@mednet.ucla.edu
authors.forename: Douglas G
authors.initials: DG
authors.lastname: Farmer
authors.forename: Bibo
authors.initials: B
authors.lastname: Ke
authors.forename: Xiu-Da
authors.initials: XD
authors.lastname: Shen
authors.forename: Fady M
authors.initials: FM
authors.lastname: Kaldas
authors.forename: Feng
authors.initials: F
authors.lastname: Gao
authors.forename: Melissa J
authors.initials: MJ
authors.lastname: Watson
authors.forename: Ronald W
authors.initials: RW
authors.lastname: Busuttil
authors.forename: Jerzy W
authors.initials: JW
authors.lastname: Kupiec-Weglinski
mesh_terms: D056704:Adaptive Immunity; D000818:Animals; D019610:Cytoprotection; D007113:Immunity, Innate; D018793:Interleukin-13 / Q000097:blood / Q000494:pharmacology*; D007422:Intestines / Q000098:blood supply*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D009195:Peroxidase / Q000378:metabolism; D011994:Recombinant Proteins / Q000494:pharmacology; D015427:Reperfusion Injury / Q000517:prevention & control*; D050800:STAT6 Transcription Factor / Q000502:physiology; D051197:Toll-Like Receptor 4 / Q000502:physiology
chemical_list: D018793:Interleukin-13; D011994:Recombinant Proteins; D050800:STAT6 Transcription Factor; C494100:Stat6 protein, mouse; C493487:Tlr4 protein, mouse; D051197:Toll-Like Receptor 4; D009195:Peroxidase