TAT-HSP70 Attenuates Experimental Lung Injury

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 the 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 Heat Shock Protein 70 (HSP70) is not increased following cecal ligation and double puncture (CLP), 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 intra-tracheal (IT) administration of HSP70 using the TAT methodology, just after CLP (CLP-TAT-HSP70), when compared to treatment with phosphate buffered saline (PBS) (CLP-PBS), significantly increased HSP70 abundance in the lung 24 and 48 h post 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 (MIP) -2 and Cytokine Induced Neutrophil Chemoattractant (CINC) -1 24 h after CLP. TATHSP70 treatment reduced Myeloperoxidase abundance 48 h post-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, IT 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.

Detection of heat shock protein 27, 70, 90 expressions in primary parenchymatous organs of goats after transport stress by real‐time PCR and ELISA

“…The heat shock response that induces HSP expression is an endogenous mechanism to protect cells from injury. The increase of HSP70 expression can be found during lung injury (Lyons, Raj, Chittams, Kilpatrick, & Deutschman, 2015). In our study, we also found that mRNA and protein levels of HSP70 in goat lung were increased after 2 hr transport.…”

Dioscin prevents LPS‑induced acute lung injury through inhibiting the TLR4/MyD88 signaling pathway via upregulation of HSP70

“…It is reported that the endogenous ligand HSP70 and HMGBI can activate TLR2 and TLR4 in the case of no pathogens, causing inflammation (11). HSP is a stress protein, as well as an endogenous protective material, and according to the molecular weight, it can be divided into HSP100, HSP90, HSP70, HSP60, HSP40 and small molecular weight HSP (26). HSP70 is a highly conserved protein expressed in the majority of organisms.…”

Protective Effect of Naringenin against Lipopolysaccharide-Induced Acute Lung Injury in Rats

“…It was reported that HSP70 significantly decreased the inflammatory biomarkers, impaired apoptotic pathways via interactions with caspases, and improved outcome after septic and shock models of ALI in rats [34,35] . In this study, LPS caused a minor insignificant upregulation of HSP70 in lung tissues.…”