Abstract
Sepsis-induced acute kidney injury (AKI) with high incidence and mortality rates remains a great challenge in the clinic; thus, novel therapies need to be developed urgently. This complication is associated with an overwhelming systemic inflammatory response. The aim of this study was to evaluate the potential effects and possible mechanisms of gold clusters on septic AKI in vitro. Rat mesangial HBZY-1 cells were treated with peptide-templated gold clusters under lipopolysaccharide (LPS) stimulation. The LPS-induced expression of pro-inflammatory cytokines was measured, including tumor necrosis factor alpha (TNF-α), interleukin-1 beta (IL-1β) and interleukin-6 (IL-6). Our data showed that the LPS-induced transcription and secretion of these cytokines were suppressed by pretreatment of gold clusters in a dose-dependent manner. Cyclooxygenase-2 (COX-2) and inducible nitric oxide synthase (iNOS) also play key roles in septic AKI and both of them are induced upon LPS-stimulation in mesangial cells. Our results further showed that pretreatment with gold clusters dramatically inhibited the LPS-stimulated transcription and expression of COX2 and iNOS, and the subsequent prostaglandin E2 (PGE2) and nitric oxide (NO) production in HBZY-1 cells. Since these factors are involved in the NF-κB pathway upon LPS stimulation, the potential roles of gold clusters on the NF-κB pathway were further determined. We found that LPS-induced NF-κB activation was suppressed in gold clusters-pretreated HBZY-1 cells. These results demonstrated that gold clusters can attenuate LPS-induced inflammation in mesangial cells, probably via inhibiting the activation of the NF-κB pathway, suggesting a potential therapeutic approach for septic AKI.
Highlights
Sepsis initiated by invasive infection is a leading cause of death in intensive care units (ICU), which is characterized by a systemic inflammatory response [1,2]
Sv peptide determined by dynamic light scattering (DLS) detection
The results showed that the LPS-induced transcriptions of IL-6, IL-1β and TNF-α were all significantly suppressed by 20 μM Au29 SG27 (Figure 5b–d)
Summary
Sepsis initiated by invasive infection is a leading cause of death in intensive care units (ICU), which is characterized by a systemic inflammatory response [1,2]. The mortality rate of sepsis is up to. 60%, and about 14,000 people die of its complications worldwide every day [3] The high mortality rate of sepsis is usually directly caused by multiple organ failure [4]. Acute kidney injury (AKI) is a common and serious complication of sepsis [5,6]. It has been reported that about half of the patients with sepsis suffer from AKI, which is a devastating disease characterized by sudden impairment of the renal function [7]. It is crucial to develop novel therapeutic approaches due to the huge health threats of AKI
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