Lipopolysaccharide-Induced Acute Kidney Injury Is Dependent on an IL-18 Receptor Signaling Pathway.

ABSTRACT: The proinflammatory cytokine interleukin (IL)-18 is an important mediator of the organ failure induced by endotoxemia. IL-18 (known as an interferon-gamma (IFN-?) inducing factor), and other inflammatory cytokines have important roles in lipopolysaccharide (LPS)-induced acute kidney injury (AKI). We investigated the effect of inflammatory cytokines and Toll-like receptor 4 (TLR4) expression, an event that is accompanied by an influx of monocytes, including CD4? T cells and antigen-presenting cells (APCs) in IL-18R? knockout (KO) mice and wild-type (WT) mice after LPS injection. In the acute advanced phase, the IL-18R? KO mice showed a higher survival rate and a suppressed increase of blood urea nitrogen, increased levels of proinflammatory cytokines such as IFN-? and IL-18, the infiltration of CD4? T cells and the expression of kidney injury molecule-1 as an AKI marker. In that phase, the renal mRNA expression of the M1 macrophage phenotype and C-C chemokine receptor type 7 as the maturation marker of dendritic cells (DCs) was also significantly decreased in the IL-18R? KO mice, although there were small numbers of F4/80? cells and DCs in the kidney. Conversely, there were no significant differences in the expressions of mRNA and protein TLR4 after LPS injection between the WT and IL-18R? KO groups. Our results demonstrated that the IL-18R?-mediated signaling pathway plays critical roles in CD4? T cells and APCs and responded more quickly to IFN-? and IL-18 than TLR4 stimulation in the pathogenesis of LPS-induced AKI.

SUBMITTER: Nozaki Y 

PROVIDER: S-EPMC5751375 | biostudies-literature | 2017 Dec

REPOSITORIES: biostudies-literature