title: Cecal ligation and double puncture impairs heat shock protein 70 (HSP-70) expression in the lungs of rats.
abstract: Induction of the heat shock response may improve outcome from pathophysiological disturbances. This improvement is associated with and believed to result from expression of heat shock protein (HSP)-70. Therefore, we examined the temporal expression of HSP-70 in an animal model of acute respiratory distress syndrome (ARDS) secondary to fecal peritonitis. Specifically, we hypothesize that sepsis in rats impairs pulmonary HSP-70 expression. ARDS was induced in adolescent rats via cecal ligation and double puncture (2CLP). Sham-operated animals served as controls. Lung tissue was collected 0, 3, 6, 16, 24, and 48 h after 2CLP and sham operation. Northern blot hybridization analysis was performed to detect steady-state HSP-70 messenger ribonucleic (mRNA) levels. HSP-70 protein levels were determined via immunoblotting and immunohistochemistry. Mortality after 2CLP was 50% at 24 h and 75% at 48 h. Northern blot hybridization analysis revealed no significant change in steady-state HSP-70 mRNA levels in lung at any time after 2CLP. HSP-70 steady-state mRNA levels increased after sham operation and was higher than values in 2CLP at 6, 16, and 24 h. HSP-70 protein levels did not change over time in either group. Thus, the expression of HSP-70 does not change after 2CLP. Although lack of an increase in protein levels may be adaptive after sham operation, it is not appropriate after 2CLP. Therefore, failed HSP-70 expression represents a form of pulmonary epithelial dysfunction that may contribute to lung injury in sepsis.
authors.affiliation: Department of Anesthesia, University of Pennsylvania School of Medicine, Philadelphia 19104-4283, USA.
authors.forename: Y G
authors.initials: YG
authors.lastname: Weiss
authors.forename: A
authors.initials: A
authors.lastname: Bouwman
authors.forename: B
authors.initials: B
authors.lastname: Gehan
authors.forename: G
authors.initials: G
authors.lastname: Schears
authors.forename: N
authors.initials: N
authors.lastname: Raj
authors.forename: C S
authors.initials: CS
authors.lastname: Deutschman
mesh_terms: D000818:Animals; D002432:Cecum; D004195:Disease Models, Animal; D005786:Gene Expression Regulation; D018840:HSP70 Heat-Shock Proteins / Q000096:biosynthesis / Q000235:genetics*; D008168:Lung / Q000378:metabolism* / Q000503:physiopathology; D008297:Male; D010538:Peritonitis / Q000235:genetics / Q000503:physiopathology*; D011677:Punctures; D051381:Rats; D017207:Rats, Sprague-Dawley; D012128:Respiratory Distress Syndrome / Q000209:etiology / Q000235:genetics / Q000503:physiopathology*; D018805:Sepsis / Q000235:genetics / Q000503:physiopathology*
chemical_list: D018840:HSP70 Heat-Shock Proteins