| First Author | Nozaki Y | Year | 2017 |
| Journal | Int J Mol Sci | Volume | 18 |
| Issue | 12 | PubMed ID | 29261164 |
| Mgi Jnum | J:273881 | Mgi Id | MGI:6282819 |
| Doi | 10.3390/ijms18122777 | Citation | Nozaki Y, et al. (2017) Lipopolysaccharide-Induced Acute Kidney Injury Is Dependent on an IL-18 Receptor Signaling Pathway. Int J Mol Sci 18(12):2777 |
| abstractText | 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-gamma) 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-18Ralpha knockout (KO) mice and wild-type (WT) mice after LPS injection. In the acute advanced phase, the IL-18Ralpha KO mice showed a higher survival rate and a suppressed increase of blood urea nitrogen, increased levels of proinflammatory cytokines such as IFN-gamma 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-18Ralpha 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-18Ralpha KO groups. Our results demonstrated that the IL-18Ralpha-mediated signaling pathway plays critical roles in CD4(+) T cells and APCs and responded more quickly to IFN-gamma and IL-18 than TLR4 stimulation in the pathogenesis of LPS-induced AKI. |
