Procalcitonin induced cytotoxicity and apoptosis in mesangial cells: implications for septic renal injury

被引：32

作者：

Araujo, Magali ^{[1
,2
]}

Doi, Sonia Q. ^{[1
]}

Palant, Carlos E. ^{[3
]}

Nylen, Eric S. ^{[4
]}

Becker, Kenneth L. ^{[4
]}

机构：

[1] Uniformed Serv Univ Hlth Sci, Bethesda, MD 20814 USA

[2] Georgetown Univ, Washington, DC USA

[3] Washington DC Vet Affairs Med Ctr, Renal Sect, Washington, DC USA

[4] George Washington Univ, Washington DC Vet Affairs Med Ctr, Med Serv, Endocrinol Sect, Washington, DC 20422 USA

来源：

INFLAMMATION RESEARCH | 2013年 / 62卷 / 10期

关键词：

Procalcitonin; Mesangial cells; Interleukin; 6; Inducible nitric oxide synthase; Apoptosis; Actin; GLOMERULAR-FILTRATION-RATE; TUMOR-NECROSIS-FACTOR; KIDNEY INJURY; NITRIC-OXIDE; SEPSIS; EXPRESSION; LIPOPOLYSACCHARIDE; RATS; FIBROSIS; GENE;

D O I：

10.1007/s00011-013-0646-8

中图分类号：

Q2 [细胞生物学];

学科分类号：

071009 ; 090102 ;

摘要：

Immuno-neutralization of procalcitonin (ProCT) has been shown to ameliorate experimental sepsis as well as the renal complications of this disease. Accordingly, we investigated the direct effect of ProCT on mesangial cells (MCs). Primary culture of murine MCs. ProCT (0.5, 1.0, 2.5, 5.0 ng/ml) for 2, 4, 6 h. MCs were exposed in vitro to ProCT. Expression levels of IL-6, iNOS and TNF-alpha were determined by real time RT-PCR, Inflammatory pathways, and a panel of cytokines and chemokines involved in the process were investigated by PCR array; apoptosis/viability were evaluated in a multiplex assay and actin cytoskeleton alterations were examined by immunofluorescence (IF). ProCT caused an early elevation in both IL-6 and iNOS mRNA (2-4 h), and a later rise (6 h) in TNF-alpha mRNA. ProCT upregulated genes of proinflammatory pathways 5- to 24-fold compared to control. IF images revealed disruption of the actin cytoskeleton and retraction of cell bodies with loss of typical stellate or spindle shape phenotype. ProCT decreased MCs viability by 36 % compared to control cells and induced significant apoptosis. ProCT has direct cytotoxic properties and may play a role in septic acute kidney injury that is independent of endotoxemia or hemodynamic alterations.

引用

页码：887 / 894

页数：8

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