Abstract
CXCL14 is a relatively novel chemokine with a wide spectrum of biological activities. The present study was designed to investigate whether CXCL14 overexpression attenuates sepsis-associated acute kidney injury (AKI) in mice. Sepsis model has been established by cecal ligation and puncture (CLP). CLP induced AKI in mice as assessed by increased renal neutrophil gelatinase-associated lipocalin (NGAL) expression and serum creatinine levels. We found that renal CXCL14 expression in the kidney was significantly decreased at 12 hours after CLP. Correlation analysis demonstrated a negative association between renal CXCL14 expression and AKI markers including serum creatinine and renal NGAL. Moreover, CXCL14 overexpression reduced cytokine (TNF-α, IL-6, and IL-1β) production and NGAL expression in the kidney and decreased serum creatinine levels. In vivo and in vitro experiments found that CXCL14 overexpression inhibited M1 macrophage polarization but increased M2 polarization. Together, these results suggest that CXCL14 overexpression attenuates sepsis-associated AKI probably through the downregulation of macrophages-derived cytokine production. However, further studies are required to elucidate the underlying mechanism.
Highlights
Sepsis is a severe condition characterized by systemic inflammatory response syndrome and the presence of infection that has fatal consequences, including acute kidney injury (AKI) [1]
Serum creatinine and renal neutrophil gelatinase-associated lipocalin (NGAL) expression were significantly increased after cecal ligation and puncture (CLP) (Figures 1(c) and 1(d))
Renal CXCL14 protein expressions were negatively associated with the production of tumor necrosis factor (TNF)-α (r = −0:984, p < 0:0001), IL-6 (r = −0:967, p < 0:0001) and IL-1β (r = −0:952, p < 0:0001) in the kidney of mice after CLP (Figures 2(d)-2(f))
Summary
Sepsis is a severe condition characterized by systemic inflammatory response syndrome and the presence of infection that has fatal consequences, including acute kidney injury (AKI) [1]. There is a very strong evidence that sepsis and septic shock are the most common causes of AKI in critically ill patients, accounting for more than 50% of AKI cases in the intensive care unit (ICU) [2]. Numerous evidences have demonstrated that the development of AKI is tightly associated with poor outcome of critically ill patients [3,4,5]. It is well established that proinflammatory cytokines, such as tumor necrosis factor-alpha (TNF-α), interleukin-1beta (IL-1β), and IL-6, contribute to the development of AKI in septic patients [7,8,9], and the inhibition of proinflammatory cytokines was able to attenuate sepsis-associated AKI and improves survival outcome [10, 11]
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