Departmental Bulletin Paper 〈Originals〉Interleukin-18 receptor α has differing roles in the systemic response and renal inflammation in lipopolysaccharide-induced acute kidney injury

Hino, Shoichi  ,  Nozaki, Yuji  ,  Nagare, Yasuaki  ,  Kinoshita, Koji  ,  Funauchi, Masanori  ,  Matsumura, Itaru

40 ( 1 )  , pp.15 - 22 , 2015-06-01 , Kinki University Medical Association
<Abstract>Interleukin (IL)-18 has important roles in the pathogenesis of organ failure caused by endotoxemia. To determine whether IL-18 receptor(R)αsignaling ameliorates or deteriorates the renal function in lipopolysaccharide (LPS)-induced acute kidney injury(AKI), we compared IL-18Rα knockout (KO) mice with wild-type (WT) mice following LPS injection. As the results, IL-18Rα deficiency ameliorated the renal function and reduced the serum level of pro-inflammatory cytokines, such as tumor necrosis factor (TNF), interferon-gamma (IFN-γ), and IL-18. The renal suppressor of cytokine signaling 1(SOCS1) mRNA expression was also significantly reduced in IL-18Rα KO mice compared with WT mice. In addition, the adoptivetransfer of splenocytes from WT mice into IL-18Rα KO mice increased their serum pro-inflammatory cytokine levels and deteriorated the renal function In conclusion, IL-18Rα deficiency ameliorated the release of systemic pro-inflammatory cytokines and renal function in mice with LPS-induced AKI. Thus, IL-18Rα affects renal injury through the pro-inflammatory cytokine signaling pathway in the pathogenesis of LPS-induced AKI.

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