Relationship between HMGB1 and tissue protective effects of HSP72 in a LPS-induced systemic inflammation model.
BACKGROUND
Heat shock protein 72 (HSP72(a)) exhibits cell- and organ-protective effects in response to inflammation. Moreover, high mobility group box 1 (HMGB1) protein is a lethal mediator of acute inflammation. We examined associations between HMGB1 expression and protective effects observed when whole-body hyperthermia (WH) induces HSP72 in a lipopolysaccharide (LPS(b))-induced inflammation model.


METHODS
Serum cytokine and HMGB1 levels, as well as HSP72 and HMGB1 expression in lung tissue were analyzed after WH treatment. Furthermore, effects of prior induction of HSP72 and silencing of HSP72 on HMGB1 secretion were examined in cultured RAW264.7 cells.


RESULTS
Survival improved significantly from 33% in the LPS group to 78% in the WH+LPS group. Interleukin-6, tumor necrosis factor-α, and HMGB1 concentrations were significantly lower in WH-treated rats. Furthermore, inflammation was reduced in lungs of WH-treated rats. Prior induction of HSP72 resulted in significantly decreased HMGB1 secretion by RAW264.7 cells in vitro, while silencing of HSP72 prevented this decrease.


CONCLUSIONS
Our results suggest that HSP72 induction by thermal pretreatment reduced inflammation and improved survival in the LPS-induced systemic inflammation model. These effects, which were associated with inhibition of HMGB1 expression, potentially involve HSP-mediated inhibition of HMGB1 secretion.
Hasegawa
Akira
A
Department of Anesthesiology and Intensive Care Medicine, Faculty of Medicine, Oita University, Yufu City, Oita, Japan. akhase@med.oita-u.ac.jp
Iwasaka
Hideo
H
Hagiwara
Satoshi
S
Noguchi
Takayuki
T
D000818:Animals; D002460:Cell Line; D005334:Fever / Q000378:metabolism*; D024243:HMGB1 Protein / Q000378:metabolism*; D050884:HSP72 Heat-Shock Proteins / Q000378:metabolism*; D007249:Inflammation / Q000139:chemically induced / Q000378:metabolism*; D015850:Interleukin-6 / Q000097:blood; D008070:Lipopolysaccharides / Q000009:adverse effects; D008168:Lung / Q000378:metabolism / Q000473:pathology; D008264:Macrophages / Q000378:metabolism / Q000473:pathology; D008297:Male; D051379:Mice; D023421:Models, Animal; D051381:Rats; D017208:Rats, Wistar; D014409:Tumor Necrosis Factor-alpha / Q000097:blood
D024243:HMGB1 Protein; D050884:HSP72 Heat-Shock Proteins; D015850:Interleukin-6; D008070:Lipopolysaccharides; D014409:Tumor Necrosis Factor-alpha