title: Release of endogenous heat shock protein 72 on the survival of sepsis in rats.
abstract: BACKGROUND
  This study was undertaken to clarify the role of extracellular heat shock protein 72 on the survival of sepsis and to determine possible factor(s) that may be responsible for it.
  
  
  METHODS
  Sepsis was induced by cecal ligation and puncture. Changes in serum levels of heat shock protein (Hsp72) and cytokines were determined during sepsis, and the results were correlated with the survival. Effects of heat pretreatment on Hsp72 expression in septic rat leukocytes and those of septic rat serum, lipopolysaccharide (LPS), and certain cytokines on the release of Hsp72 in macrophage NR8383 cells were determined.
  
  
  RESULTS
  Circulating Hsp72 levels were increased during the progress of sepsis (0, 5.5, 6.5, 10, and 6.5 ng/mL at 0, 3, 6, 9, and 18 h after cecal ligation and puncture, respectively) and the increases were correlated positively with survival rates. LPS triggered the release of Hsp72 in heat pretreated animals. Heat pretreatment increased Hsp72 expression in nonsepsis (+535%, P < 0.01) and sepsis (+116%, P<0.01%) rat leukocytes. Incubation of sepsis rat serum with NR8383 cells increased levels of extracellular heat shock protein 72 in cultured medium. Cytokine profiling revealed that among the 19 cytokines screened, four of them were increased as follows: cytokine-induced neutrophil chemoattractant 3 (+211.3%, P < 0.05), interleukin 10 (+147%, P < 0.05), MCP-1 (+49.6%, P < 0.05), and tumor necrosis factor alpha (+51.8%, P < 0.05). MCP-1 and LPS were capable of releasing Hsp72 from NR8383 cells.
  
  
  CONCLUSIONS
  These results demonstrate that the increases in the levels of circulating Hsp72 had a beneficial effect in improving animal survival during the progress of sepsis. The increases in circulating Hsp72 may be mediated via MCP-1 and/or LPS.
authors.affiliation: Graduate Institute of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan.
authors.forename: Tsen-Ni
authors.initials: TN
authors.lastname: Tsai
authors.affiliation: Graduate Institute of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan.
authors.forename: Tzu-Ying
authors.initials: TY
authors.lastname: Lee
authors.affiliation: Graduate Institute of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan; Department of Physiology, College of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan.
authors.forename: Maw-Shung
authors.initials: MS
authors.lastname: Liu
authors.affiliation: Department of Respiratory Therapy, Kaohsiung Medical University, Kaohsiung, Taiwan.
authors.forename: I-Chun
authors.initials: IC
authors.lastname: Chuang
authors.affiliation: Graduate Institute of Marine Biotechnology, National Dong Hwa University, Pingtung, Taiwan.
authors.forename: Mei-Chin
authors.initials: MC
authors.lastname: Lu
authors.affiliation: Department of Physical Therapy, Fooyin University, Kaohsiung, Taiwan.
authors.forename: Huei-Ping
authors.initials: HP
authors.lastname: Dong
authors.affiliation: Department of Physiology, College of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan.
authors.forename: Sheng-I
authors.initials: SI
authors.lastname: Lue
authors.affiliation: Graduate Institute of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan; Department of Pediatrics, Kaohsiung Medical University Hospital, Kaohsiung, Taiwan; Department of Pediatrics, Changhua Christian Hospital, Changhua, Taiwan. Electronic address: rechya@kmu.edu.tw.
authors.forename: Rei-Chen
authors.initials: RC
authors.lastname: Yang
mesh_terms: D000818:Animals; D002460:Cell Line; D018932:Chemokine CCL2 / Q000502:physiology; D016207:Cytokines / Q000032:analysis; D050884:HSP72 Heat-Shock Proteins / Q000502:physiology*; D007962:Leukocytes / Q000737:chemistry; D008070:Lipopolysaccharides / Q000633:toxicity; D008297:Male; D051381:Rats; D017207:Rats, Sprague-Dawley; D018805:Sepsis / Q000276:immunology / Q000401:mortality*
chemical_list: C491766:Ccl2 protein, rat; D018932:Chemokine CCL2; D016207:Cytokines; D050884:HSP72 Heat-Shock Proteins; D008070:Lipopolysaccharides
keywords: Extracellular heat shock protein 72; Lipopolysaccharide; Monocyte chemotactic/chemoattractant protein-1; Sepsis