The Yin and Yang of Alarmins in Regulation of Acute Kidney Injury

Abstract

Acute kidney injury (AKI) is a major clinical burden affecting 20 to 50% of hospitalized and intensive care patients. Irrespective of the initiating factors, the immune system plays a major role in amplifying the disease pathogenesis with certain immune cells contributing to renal damage, whereas others offer protection and facilitate recovery. Alarmins are small molecules and proteins that include granulysins, high-mobility group box 1 protein, interleukin (IL)-1α, IL-16, IL-33, heat shock proteins, the Ca ++ binding S100 proteins, adenosine triphosphate, and uric acid. Alarmins are mostly intracellular molecules, and their release to the extracellular milieu signals cellular stress or damage, generally leading to the recruitment of the cells of the immune system. Early studies indicated a proinflammatory role for the alarmins by contributing to immune-system dysregulation and worsening of AKI. However, recent developments demonstrate anti-inflammatory mechanisms of certain alarmins or alarmin-sensing receptors, which may participate in the prevention, resolution, and repair of AKI. This dual function of alarmins is intriguing and has confounded the role of alarmins in AKI. In this study, we review the contribution of various alarmins to the pathogenesis of AKI in experimental and clinical studies. We also analyze the approaches for the therapeutic utilization of alarmins for AKI.

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“…Histones in the bloodstream could also be interpreted as a sign of netosis and formation of neutrophil extracellular traps (NETS) (Papayannopoulos, 2018). HSPs have also been identified as DAMPs produced by a number of tissues upon injury, including liver (Martin-Murphy et al, 2010) and kidney (Sabapathy et al, 2020), further exacerbating inflammation at the damaged tissue.…”

Identification of inflammatory response and alternative splicing in acute kidney injury and experimental verification of the involvement of RNA‑binding protein RBFOX1 in this disease

“…AKI is described as an inflammatory disease and inflammatory factors are involved in its damage and repair process ( 30 ). TLR2 was originally considered to be a proinflammatory factor, but a recent study revealed that it can play a protective role in AKI by activating autophagy ( 31 ).…”

Endogenous Interleukin-33 Acts as an Alarmin in Liver Ischemia-Reperfusion and Is Associated With Injury After Human Liver Transplantation

“…Mechanisms that can be put at stake in acute kidney injury after liver transplantation involving IL-33 are the recruitment of myeloid cells through monocyte chemoattractant protein-1 and macrophage inflammatory protein-2, and the recruitment of neutrophils either directly or via the activation of invariant natural killer T (iNKT) cells ( 38 ).…”