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논문분류	춘계학술대회 초록집
제목	Regulatory T Cells Recruited to the Kidney by N,N-dimethylsphingosine Ameliorate Lipopolysaccharide-induced Acute Kidney Injury
저자	Ko Eun Lee1, In Jin Kim2, Hoon In Choi2, Chang Seong Kim1, Joon Seok Choi1, Eun Hui Bae1, Seong Kwon Ma1, Jong Un Lee2, Soo Wan Kim1
출판정보	2013; 2013(1):
키워드	Acute kidney injury, DMS, LPS
초록	Objective: Regulatory T cells (Tregs) play a role in immunologic tolerance and have the potential to prevent inflammatory diseases by suppress immune responses. The purpose of this study was to examine the effect of N,N-dimethylsphingosine (DMS), a sphingosine kinase inhibitor, on lipopolysaccharide (LPS)-induced kidney inflammation and to explore the underlying molecular mechanisms. Materials & Methods: Mice were treated LPS (100 mg/kg, intraperitoneally) with or without pretreatment with DMS (0.4 mg/kg, intraperitoneally). The expression of cyclooxygenase-2 (COX-2), inducible nitric oxide synthase (iNOS), and endothelin-1 (ED-1) was determined by immunoblotting and immunohistochemical staining. The mRNA level of interleukin-1β (IL-1β), interleukin-6 (IL-6), tumor necrosis factor-α (TNF-α), monocyte chemoattractant protein-1 (MCP-1), interferon-γ (IFN-γ), and Foxp3 was measured by real-time PCR. Using flow cytometry analysis, we investigated the expression of CD4+ CD25+ Tregs in mice spleen. Results: Plasma creatinine level was increased after LPS injection for 12 h compared with controls, which was attenuated in pretreatment with DMS. LPS upregulated CD4+ CD25+ Treg in the spleen, but downregulated Foxp3 mRNA level in the kidney. DMS induced both CD4+ CD25+ Tregs in the spleen and the level of Foxp3 in the kidney. The expression of COX-2, iNOS, and ED-1 in mice kidneys was increased in LPS group, which was downregulated by DMS pretreatment. LPS-induced increased mRNA expression of IL-1β, IL-6, MCP-1 and IFN-γ mRNA was attenuated by DMS pretreatment. Conclusions: DMS ameliorates inflammation in LPS-induced kidney injury by decreasing inflammatory cytokines production, modulating infiltration of Tregs from spleen to kidney. Thus, DMS may protect against the acute kidney injury caused by LPS.
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