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2015 ; 43
(6
): 582-8
Nephropedia Template TP
Lyons MM
; Raj NN
; Chittams JL
; Kilpatrick L
; Deutschman CS
Shock
2015[Jun]; 43
(6
): 582-8
PMID25664981
show ga
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.
|Animals
[MESH]
|Chemokine CXCL2/metabolism
[MESH]
|HSP70 Heat-Shock Proteins/*therapeutic use
[MESH]
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