{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,1]],"date-time":"2026-10-01T16:58:08Z","timestamp":1790873888523,"version":"4.1.0"},"reference-count":49,"publisher":"MDPI AG","issue":"12","license":[{"start":{"date-parts":[[2017,12,20]],"date-time":"2017-12-20T00:00:00Z","timestamp":1513728000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>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-\u03b3) 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\u03b1 knockout (KO) mice and wild-type (WT) mice after LPS injection. In the acute advanced phase, the IL-18R\u03b1 KO mice showed a higher survival rate and a suppressed increase of blood urea nitrogen, increased levels of proinflammatory cytokines such as IFN-\u03b3 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\u03b1 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\u03b1 KO groups. Our results demonstrated that the IL-18R\u03b1-mediated signaling pathway plays critical roles in CD4+ T cells and APCs and responded more quickly to IFN-\u03b3 and IL-18 than TLR4 stimulation in the pathogenesis of LPS-induced AKI.<\/jats:p>","DOI":"10.3390\/ijms18122777","type":"journal-article","created":{"date-parts":[[2017,12,20]],"date-time":"2017-12-20T11:34:14Z","timestamp":1513769654000},"page":"2777","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":32,"title":["Lipopolysaccharide-Induced Acute Kidney Injury Is Dependent on an IL-18 Receptor Signaling Pathway"],"prefix":"10.3390","volume":"18","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-2810-1519","authenticated-orcid":false,"given":"Yuji","family":"Nozaki","sequence":"first","affiliation":[{"name":"Department of Hematology and Rheumatology, Kindai University Faculty of Medicine, Osaka-sayama, Osaka 589-8511, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shoichi","family":"Hino","sequence":"additional","affiliation":[{"name":"Department of Hematology and Rheumatology, Kindai University Faculty of Medicine, Osaka-sayama, Osaka 589-8511, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jinhai","family":"Ri","sequence":"additional","affiliation":[{"name":"Department of Hematology and Rheumatology, Kindai University Faculty of Medicine, Osaka-sayama, Osaka 589-8511, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kenji","family":"Sakai","sequence":"additional","affiliation":[{"name":"Department of Hematology and Rheumatology, Kindai University Faculty of Medicine, Osaka-sayama, Osaka 589-8511, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yasuaki","family":"Nagare","sequence":"additional","affiliation":[{"name":"Department of Hematology and Rheumatology, Kindai University Faculty of Medicine, Osaka-sayama, Osaka 589-8511, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mai","family":"Kawanishi","sequence":"additional","affiliation":[{"name":"Department of Hematology and Rheumatology, Kindai University Faculty of Medicine, Osaka-sayama, Osaka 589-8511, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kaoru","family":"Niki","sequence":"additional","affiliation":[{"name":"Department of Hematology and Rheumatology, Kindai University Faculty of Medicine, Osaka-sayama, Osaka 589-8511, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Masanori","family":"Funauchi","sequence":"additional","affiliation":[{"name":"Department of Hematology and Rheumatology, Kindai University Faculty of Medicine, Osaka-sayama, Osaka 589-8511, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Itaru","family":"Matsumura","sequence":"additional","affiliation":[{"name":"Department of Hematology and Rheumatology, Kindai University Faculty of Medicine, Osaka-sayama, Osaka 589-8511, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2017,12,20]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"143","DOI":"10.1016\/S1074-7613(00)80596-8","article-title":"Targeted disruption of the MyD88 gene results in loss of IL-1- and IL-18-mediated function","volume":"9","author":"Adachi","year":"1998","journal-title":"Immunity"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"206","DOI":"10.1016\/S0167-5699(00)01611-X","article-title":"The IL-1 receptor\/toll-like receptor superfamily: Crucial receptors for inflammation and host defense","volume":"21","author":"Dinarello","year":"2000","journal-title":"Immunol. 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