title: Ischemic Preconditioning-Induced SOCS-1 Protects Rat Intestinal Ischemia Reperfusion Injury via Degradation of TRAF6.
abstract: The inflammatory immune response plays an important role in mesenteric ischemia and ischemia-reperfusion injury. Toll-like receptor 4 (TLR4) is a critical receptor in transduction of the inflammatory response and plays an important role in intestinal homeostasis. Tumor necrosis factor receptor-associated factor 6 (TRAF6), known as a key adaptor protein downstream of TLR4, is involved in the inflammatory response by activating multiple apoptotic signaling pathways. However, mechanisms of the suppressor of cytokine signaling-1 (SOCS-1) in regulating cell inflammation and apoptosis are still obscure.
  
  
  
  To investigate the TLR4-TRAF6 signaling pathway in intestinal ischemia and reperfusion injury, as well as SOCS-1 expression after ischemic preconditioning in the rat intestine.
  
  
  
  The small bowel ischemia, ischemia-reperfusion, and preconditioning models were induced using ligation of the superior mesenteric artery in male Sprague-Dawley rats; then, the mRNA and protein levels of TLR4, TRAF6, and SOCS-1 were analyzed using real-time PCR, Western blot, and immunohistochemistry, respectively.
  
  
  
  The expression of TLR4 and TRAF6 was gradually increased with increasing intestinal ischemia duration, but increased substantially after ischemia-reperfusion injury. After ischemic preconditioning, TLR4 and TRAF6 expressions decreased; however, expression of SOCS-1 and the TLR4-TRAF6 pathway inhibitor was increased.
  
  
  
  These data show that ischemic preconditioning may induce the activation of SOCS-1 to inhibit the TLR4-TRAF6 signaling pathway, thereby playing a protective role in ischemia-reperfusion injury.
authors.affiliation: SouthWest Medical University Clinical Medicine, 25 Tai Ping Street, Lu Zhou, 646000, Sichuan Province, People's Republic of China.|Department of Vascular Surgery, The Second People's Hospital of Yibin, 96 North Street, Yi Bin, 644000, Sichuan Province, People's Republic of China.
authors.forename: Sheng-Zhi
authors.initials: SZ
authors.lastname: Liu
authors.affiliation: Medical Research Center, The Affiliated Hospital of SouthWest Medical University, 25 Tai Ping Street, Lu Zhou, 646000, Sichuan Province, People's Republic of China.
authors.forename: Xue-Mei
authors.initials: XM
authors.lastname: He
authors.affiliation: Department of Pathology, The Affiliated Hospital of SouthWest Medical University, 25 Tai Ping Street, Lu Zhou, 646000, Sichuan Province, People's Republic of China.
authors.forename: Xu
authors.initials: X
authors.lastname: Zhang
authors.affiliation: Department of Biochemistry, SouthWest Medical University, 25 Tai Ping Street, Lu Zhou, 646000, Sichuan Province, People's Republic of China.
authors.forename: Fan-Cai
authors.initials: FC
authors.lastname: Zeng
authors.affiliation: Department of Vascular and Thyroid Surgery, The Affiliated Hospital of SouthWest Medical University, 25 Tai Ping Street, Lu Zhou, 646000, Sichuan Province, People's Republic of China.
authors.forename: Fang
authors.initials: F
authors.lastname: Wang
authors.affiliation: Department of Vascular and Thyroid Surgery, The Affiliated Hospital of SouthWest Medical University, 25 Tai Ping Street, Lu Zhou, 646000, Sichuan Province, People's Republic of China. xiangyuzhou971@126.com.
authors.forename: Xiang-Yu
authors.initials: XY
authors.lastname: Zhou
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000276:immunology; D015153:Blotting, Western; D007150:Immunohistochemistry; D020287:In Situ Nick-End Labeling; D007421:Intestine, Small / Q000276:immunology* / Q000473:pathology; D019194:Ischemic Preconditioning; D008026:Ligation; D008297:Male; D017538:Mesenteric Artery, Superior / Q000601:surgery; D065666:Mesenteric Ischemia / Q000276:immunology* / Q000473:pathology; D017346:Protein Serine-Threonine Kinases / Q000235:genetics / Q000276:immunology; D051381:Rats; D017207:Rats, Sprague-Dawley; D060888:Real-Time Polymerase Chain Reaction; D053422:Receptor-Interacting Protein Serine-Threonine Kinases; D015427:Reperfusion Injury / Q000276:immunology* / Q000473:pathology; D015398:Signal Transduction; D000071222:Suppressor of Cytokine Signaling 1 Protein / Q000235:genetics / Q000276:immunology*; D048029:TNF Receptor-Associated Factor 6 / Q000235:genetics / Q000276:immunology*; D051197:Toll-Like Receptor 4 / Q000235:genetics / Q000276:immunology*
chemical_list: C491589:Socs1 protein, rat; D000071222:Suppressor of Cytokine Signaling 1 Protein; D048029:TNF Receptor-Associated Factor 6; C495347:Tlr4 protein, rat; D051197:Toll-Like Receptor 4; D017346:Protein Serine-Threonine Kinases; C586536:RIPK1 protein, rat; D053422:Receptor-Interacting Protein Serine-Threonine Kinases
keywords: Apoptosis; Cell signaling inhibition of apoptosis factor 1; Intestinal ischemia–reperfusion; Ischemic preconditioning; Tumor necrosis factor receptor-associated factor 6