Publication Date
2015
Journal Title
Shock
Abstract
Sepsis, a poorly understood syndrome of disordered inflammation, is the leading cause of death in critically ill patients. Lung injury, in the form of acute respiratory distress syndrome (ARDS), is the most common form of organ injury in sepsis. The heat shock response, during which heat shock proteins (HSPs) are expressed, is an endogenous mechanism to protect cells from injury. We have found that the abundance of pulmonary HSP70 is not increased after cecal ligation and double puncture (CLP) in a rat model of sepsis-induced ARDS. Using the HIV-1 trans-activator of transcription (TAT) cell-penetrating protein, we enhanced HSP70 protein abundance in the lung. We found that intratracheal administration of HSP70 using the TAT methodology, just after CLP (CLP-TAT-HSP70), when compared with treatment with phosphate buffered saline (CLP-phosphate buffered saline), significantly increased HSP70 abundance in the lung 24 and 48 h after surgery. Treatment of septic rats with TAT-HSP70 increased HSP70 abundance in histologically normal and abnormal lung regions. In addition, TAT-HSP70 treatment significantly decreased the levels of macrophage inflammatory protein 2 and cytokine-induced neutrophil chemoattractant 1 24 h after CLP. The TAT-HSP70 treatment reduced myeloperoxidase abundance 48 h after CLP and attenuated histological evidence of inflammation at both 24 and 48 h. Administration of TAT-HSP70 also improved 48-h survival in this rat model of sepsis. Thus, intratracheal administration of TAT-HSP70 increased HSP70 abundance in the lung and attenuated the lung injury. Enhancing pulmonary HSP70 using TAT is a novel potential therapeutic strategy for the treatment of ARDS that will be explored further.
Volume Number
43
Issue Number
6
Pages
582-588
Document Type
Article
Status
Faculty
Facility
School of Medicine
Primary Department
General Pediatrics
Additional Departments
Molecular Medicine
PMID
DOI
10.1097/shk.0000000000000352