title: Adenosine A2B receptor modulates intestinal barrier function under hypoxic and ischemia/reperfusion conditions.
abstract: BACKGROUND
  Intestinal barrier function failure from ischemia/reperfusion (I/R) and acute hypoxia has been implicated as a critical determinant in the predisposition to intestinal inflammation and a number of inflammatory disorders. Here, we identified the role of Adenosine A2B receptor (A2BAR) in the regulation of intestinal barrier function under I/R and acute hypoxic conditions.
  
  
  METHODS
  C57BL/6J mice were used, and were randomized into three groups: Sham, I/R, IR+PSB1115 (a specific A2BAR antagonist) groups. After surgery, the small bowel was harvested for immunohistochemical staining, RNA and protein content, and intestinal permeability analyses. Using an epithelial cell culture model, we investigated the influence of hypoxia on the epithelial function, and the role of A2BAR in the expressions of tight junction and epithelial permeability. The expressions of Claudin-1, occludin and ZO-1 were detected by RT-PCR and Western-Blot. Epithelial barrier function was assessed with transepithelial resistance (TER).
  
  
  CONCLUSIONS
  The A2BAR antagonist, PSB1115, significantly increased tight junction protein expression after intestinal I/R or acute hypoxia conditions. PSB1115 also attenuated the disrupted distribution of TJ proteins. Furthermore, inhibition of A2BAR attenuated the decrease in TER induced by I/R or acute hypoxic conditions, and maintained intestinal barrier function. Antagonism of A2BAR activity improves intestinal epithelial structure and barrier function in a mouse model of intestinal I/R and a cell model of acute hypoxia. These findings support a potentially destructive role for A2BAR under intestinal I/R and acute hypoxic conditions.
authors: Department of General Surgery, Xinqiao Hospital, Third Military Medical University Chongqing, China.
authors: Yang
authors: Y
authors: Yang
authors: Department of General Surgery, Xinqiao Hospital, Third Military Medical University Chongqing, China.
authors: Yuan
authors: Y
authors: Qiu
authors: Department of General Surgery, Xinqiao Hospital, Third Military Medical University Chongqing, China.
authors: Wensheng
authors: W
authors: Wang
authors: Department of General Surgery, Xinqiao Hospital, Third Military Medical University Chongqing, China.
authors: Weidong
authors: W
authors: Xiao
authors: Department of General Surgery, Xinqiao Hospital, Third Military Medical University Chongqing, China.
authors: Hongyin
authors: H
authors: Liang
authors: Department of General Surgery, Xinqiao Hospital, Third Military Medical University Chongqing, China.
authors: Chaojun
authors: C
authors: Zhang
authors: University of Michigan Ann Arbor, MI, USA.
authors: Hanwenbo
authors: H
authors: Yang
authors: Department of Surgery, University of Michigan MI, USA.
authors: Daniel H
authors: DH
authors: Teitelbaum
authors: Department of General Surgery, Xinqiao Hospital, Third Military Medical University Chongqing, China.
authors: Li-Hua
authors: LH
authors: Sun
authors: Department of General Surgery, Xinqiao Hospital, Third Military Medical University Chongqing, China.
authors: Hua
authors: H
authors: Yang
mesh_terms: D000208:Acute Disease; D058917:Adenosine A2 Receptor Antagonists / Q000494:pharmacology; D000818:Animals; D018938:Caco-2 Cells; D004195:Disease Models, Animal; D017097:Electric Impedance; D006801:Humans; D000860:Hypoxia / Q000235:genetics / Q000378:metabolism*; D007421:Intestine, Small / Q000098:blood supply* / Q000187:drug effects / Q000378:metabolism*; D008297:Male; D008810:Mice, Inbred C57BL; D010539:Permeability; D012333:RNA, Messenger / Q000378:metabolism; D043704:Receptor, Adenosine A2B / Q000187:drug effects / Q000235:genetics / Q000378:metabolism*; D015427:Reperfusion Injury / Q000235:genetics / Q000378:metabolism*; D015398:Signal Transduction; D062725:Tight Junction Proteins / Q000235:genetics / Q000378:metabolism; D019108:Tight Junctions / Q000378:metabolism; D013997:Time Factors
chemical_list: D058917:Adenosine A2 Receptor Antagonists; D012333:RNA, Messenger; D043704:Receptor, Adenosine A2B; D062725:Tight Junction Proteins
keywords: Ischemia/reperfusion; TER; ZO-1; adenosine A2B receptor; claudin-1; hypoxia; occludin; tight junction