Mediators of Inflammation in Acute Kidney Injury

Abstract

Acute kidney injury (AKI) remains to be an independent risk factor for mortality and morbidity. Inflammation is now believed to play a major role in the pathopathophysiology of AKI. It is hypothesized that in ischemia, sepsis and nephrotoxic models that the initial insult results in morphological and/or functional changes in vascular endothelial cells and/or in tubular epithelium. Then, leukocytes including neutrophils, macrophages, natural killer cells, and lymphocytes infiltrate into the injured kidneys. The injury induces the generation of inflammatory mediators like cytokines and chemokines by tubular and endothelial cells which contribute to the recruiting of leukocytes into the kidneys. Thus, inflammation has an important role in the initiation and extension phases of AKI. This review will focus on the mediators of inflammation contributing to the pathogenesis of AKI.

14S,21R-dihydroxy-docosahexaenoic Acid Treatment Enhances Mesenchymal Stem Cell Amelioration of Renal Ischemia/Reperfusion Injury

“…Inflammation caused by leukocytes plays an important role in I/R injury [20]. To investigate whether antiinflammatory mechanisms were involved in the enhancement of MSC actions, we assessed neutrophil, macrophage, and DC infiltration of kidneys at days 1 and 3 post-I/R.…”

“…14S,21R-diHDHA treatment enhances mMSC anti-inflammatory function in vitro by suppressing the generation of inflammatory cytokines and ROS in RAW264.7 macrophages Acute kidney injury has been shown to induce macrophages to produce inflammatory cytokines and ROS that play crucial roles in inflammation and injury processes of kidneys [20,28]. In order to determine whether 14S,21R-diHDHA treatment enhances MSC anti-inflammatory function, we studied the effect of 14S,21R-diHDHA-treated MSCs on the generation of inflammatory cytokines and ROS by RAW264.7 macrophages under I/R conditions.…”

“…Renal I/R injury induces secretion of inflammatory cytokines, chemokines, and other factors, which recruit neutrophils, macrophages, and dendritic cells (DCs) to the kidneys [20,21]. Inflammatory leukocytes generate more inflammatory cytokines, amplify the renal injury, and contribute to tubular cell apoptosis and necrosis [20].…”

“…Inflammatory leukocytes generate more inflammatory cytokines, amplify the renal injury, and contribute to tubular cell apoptosis and necrosis [20]. The renal reparative manifestation of MSCs involves their anti-inflammatory functions [9,15].…”

“…Although MSCs possess the capability to ameliorate acute kidney injury, the low viability of transplanted cells in I/R injured organs remains an important limitation for MSC therapy [2,27]. Reactive oxygen species (ROS) and inflammatory cytokines generated in I/R are the probable source of damage to the grafted MSCs [8,20]. Several remedial approaches have been recommended to overcome MSC apoptosis [2], including ischemic or cytokine preconditioning and ex vivo genetic modification of stem cells.…”