Human heat shock protein 27 exacerbates ischemia reperfusion injury in rats by reducing the number of T regulatory cells

Abstract

Ischemia reperfusion injury (IRI) occurs in almost every liver surgery and is associated with the reduction of the liver blood flow. Ischemia impairs liver function and can even cause liver failure following surgery. The present study aimed to identify a new molecular target allowing the reduction of IRI and explore the related cellular mechanism. Adenovirus (~2.5x10(12) viral particles) bearing the human heat shock protein 27 (HSP27) gene was injected into rat liver through the ileocecal vein. Five days following the injection, ischemia was induced by clamping the median and left portal veins, hepatic arteries and bile ducts. The levels of alanine transaminase (ALT), aspartate aminotransferase (AST), glutathione (GSH) and superoxide dismutase (SOD) were measured. The infiltration of inflammatory cells and the expression of pro-inflammatory factors were investigated. The number of regulatory T cells (Tregs) was measured by flow cytometry. At 2 h following reperfusion, the group injected with HSP27 had the highest level of ALT and AST, followed by the group injected with HSP27 and treated with gadolinium trichloride (GdCl3), the empty vector-injected and the vector+GdCl3 groups. The HSP27 group also had the lowest levels of the oxidative stress-protective factors SOD and GSH, and the highest levels of pro-inflammatory factors. The number of Tregs was reduced in the groups injected with HSP27. In conclusion, the human HSP27 protein can effectively accelerate liver damage at the early stages of IRI in rats. Tregs might play a critical role in HSP27‑induced liver injury.

The Immune Pathogenesis of Acute-On-Chronic Liver Failure and the Danger Hypothesis

“…Ye et al. found that HSP27 accelerated the early acute liver injury induced by ischemia–reperfusion injury in rats by reducing the number of Treg cells, reducing levels of the stress-protective factors superoxide dismutase (SOD) and glutathione, increasing the level of proinflammatory factors, and aggravating inflammation ( 73 ). Wright et al.…”

“…Most scholars believe that HSPs are important protective factors in the repair of liver tissue damage and that increases in their levels are helpful for the prognosis of patients and predicting efficacy, but the mechanism of some remains controversial. Ye et al found that HSP27 accelerated the early acute liver injury induced by ischemia-reperfusion injury in rats by reducing the number of Treg cells, reducing levels of the stress-protective factors superoxide dismutase (SOD) and glutathione, increasing the level of proinflammatory factors, and aggravating inflammation (73). Wright et al conducted ACLF-related animal experiments and showed increased HSP25 in the corpus callosum of the bile duct ligation (BDL) rat model, suggesting a cell stress state (such as inflammation and apoptosis) (87).…”