Interleukin 1 Receptor (IL-1R1) Activation Exacerbates Toxin-Induced Acute Kidney Injury.

Interleukin 1 Receptor (IL-1R1) Activation Exacerbates Toxin-Induced Acute Kidney Injury. Am J Physiol Renal Physiol. 2018 May 23;: Authors: Privratsky JR, Zhang J, Lu X, Rudemiller N, Wei Q, Yu YR, Gunn MD, Crowley SD Abstract Acute kidney injury (AKI) is a leading cause of morbidity and mortality. Cisplatin is an effective chemotherapeutic agent whose administration is limited by nephrotoxicity. Therapies to prevent cisplatin-induced AKI are lacking. While tumor necrosis factor-α (TNF) plays a key role in the pathogenesis of cisplatin nephrotoxicity, the immune signaling pathways that trigger TNF generation in this context require elucidation. Sterile injury triggers the release and activation of both isoforms of interleukin(IL)-1, IL-1α and IL-1β, and stimulation of the interleukin-1 receptor (IL-1R1) by these ligands engages a pro-inflammatory signaling cascade that induces TNF induction. We therefore hypothesized that IL-1R1 activation exacerbates cisplatin-induced AKI by inducing TNF production thereby augmenting inflammatory signals between kidney parenchymal cells and infiltrating myeloid cells. IL-1R1+/+ (WT) and IL-1R1-/- (KO) mice were subjected to cisplatin-induced AKI. Compared to WT mice, IL-1R1 KO mice had attenuated AKI as measured by serum creatinine and BUN; renal NGAL mRNA levels; and blinded histological analysis of kidney pathology. In the cisplatin-injured kidney, IL-1R1 KO mice had diminished levels of whole...
Source: Am J Physiol Renal P... - Category: Urology & Nephrology Authors: Tags: Am J Physiol Renal Physiol Source Type: research