Abstract
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, 5.0ng/ml) for 2, 4, 6h. MCs were exposed in vitro to ProCT. Expression levels of IL-6, iNOS and TNF-α 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 (2-4h), and a later rise (6h) in TNF-α 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.
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