Podocytes express IL-6 and lipocalin 2/ neutrophil gelatinase-associated lipocalin in lipopolysaccharide-induced acute glomerular injury.

Podocytes express IL-6 and lipocalin 2/ neutrophil gelatinase-associated lipocalin in lipopolysaccharide-induced acute glomerular injury.
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DOI:
10.1159/000345151
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发表时间:
2012
期刊:
Nephron. Experimental nephrology
影响因子:
--
通讯作者:
Cunard R
Cunard R
中科院分区:
其他
文献类型:
--
作者:
Lee SJ;Borsting E;Declèves AE;Singh P;Cunard R

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急性肾损伤(AKI)是重症监护病房(ICU)发病率和死亡率的重要组成部分。血浆白细胞介素(IL)-6水平预测AKI的发展,并与ICU AKI患者较高的死亡率相关。尽管有证据表明AKI累及肾小球,但大多数AKI研究都集中在小管间质上。在接下来的研究中,我们的目的是研究IL-6及其下游介质在败血症诱导的AKI中的表达。采用体外脂多糖(LPS)处理足细胞和小鼠,通过实时荧光定量PCR、ELISA和原位RNA杂交检测IL-6的表达。在LPS刺激下,IL-6在培养足细胞和体内肾小球及浸润性白细胞中迅速和高度诱导。令人惊讶的是,在对外源性IL-6的直接反应中,足细胞产生脂钙素-2/中性粒细胞明胶酶相关脂钙素(Lcn2/Ngal)。LPS还能诱导培养足细胞和体内肾小球中ln2 /Ngal的表达。在IL-6敲除小鼠中也观察到强烈的Lcn2/Ngal表达,这表明虽然IL-6可能足以诱导肾小球Lcn2/Ngal表达,但不是必需的。肾小球参与脓毒性AKI,我们证明足细胞分泌AKI的关键介质包括IL-6和Lcn2/Ngal。
Acute kidney injury (AKI) contributes to significant morbidity and mortality in the intensive care unit (ICU). Plasma levels of interleukin (IL)-6 predict the development of AKI and are associated with higher mortality in ICU patients with AKI. Most studies in AKI have focused on the tubulo-interstitium, despite evidence of glomerular involvement. In the following study, our goals were to investigate the expression of IL-6 and its downstream mediators in septic-induced AKI. Podocytes were treated in vitro with lipopolysaccharide (LPS) and mice were treated with LPS, and we evaluated IL-6 expression by real-time PCR, ELISA and in situ RNA hybridization. Following LPS stimulation, IL-6 is rapidly and highly induced in cultured podocytes and in vivo in glomeruli and infiltrating leukocytes. Surprisingly, in direct response to exogenous IL-6, podocytes produce lipocalin-2/neutrophil gelatinase-associated lipocalin (Lcn2/Ngal). LPS also potently induces Lcn2/Ngal expression in podocytes in culture and in glomeruli in vivo. Intense Lcn2/Ngal expression is also observed in IL-6 knockout mice, suggesting that while IL-6 may be sufficient to induce glomerular Lcn2/Ngal expression, it is not essential. The glomerulus is involved in septic AKI, and we demonstrate that podocytes secrete key mediators of AKI including IL-6 and Lcn2/Ngal.
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