Olaparib attenuates sepsis-induced acute multiple organ injury via ERK-mediated CD14 expression

Abstract

Sepsis is characterized by persistent systemic inflammation, which can cause multi-organ dysfunction. The poly polymerase-1 inhibitor olaparib possesses anti-inflammatory properties. This study aimed to assess the effects of olaparib (pre- and post-treatments) on sepsis, and to investigate whether it could suppress CD14 expression via the ERK pathway in polymicrobial sepsis and peritoneal macrophages models. Sepsis was induced by cecal ligation and puncture in C57BL/6 male mice. Fifty mice were randomly divided into five groups: The sham group was treated with vehicle or olaparib, the cecal ligation and puncture group with vehicle or with olaparib (5 mg/kg i.p.) 1 h before or 2 h after surgery. Olaparib pretreatment significantly improved the survival of septic mice (P < 0.001). Pre- and post-treatment of mice with olaparib partly alleviated cecal ligation and puncture-induced organ injury by decreasing the amounts of the pro-inflammatory mediators TNF-α and IL-6 as well as bacterial burden in the serum, peritoneal lavage fluid, and organs (P < 0.05). The protective effect of olaparib was associated with CD14 suppression via inhibition of ERK activation. Olaparib facilitated negative regulation of ERK-mediated CD14 expression, which may contribute to multi-organ injury in sepsis.