Klotho expression is reduced in COPD airway epithelial cells: effects on inflammation and oxidant injury.
Bottom Line: Moreover, the effect of KL on CSE-mediated inflammation and hydrogen peroxide-induced cellular injury/apoptosis was determined using siRNAs.CSE and TNFα (tumour necrosis factor α) decreased KL expression and release from airway epithelial cells, which was associated with enhanced pro-inflammatory cytokine expression.These effects involved the NF-κB (nuclear factor κB), MAPK (mitogen-activated protein kinase) and Nrf2 (nuclear factor erythroid 2-related factor 2) pathways.
Affiliation: Department of Respiratory Medicine, The First Affiliated Hospital of Nanjing Medical University, 300 Guangzhou Road, Nanjing 210029, China.Show MeSH
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Mentions: In reverse experiments, we examined the effect of KL knockdown on epithelial cell function by using selective siRNAs. KL knockdown resulted in an 80–95% suppression of KL protein and mRNA expression, with siRNA3 being the most effective (Figure 5A). KL knockdown showed a small, but significant, decrease in cell viability compared with the control siRNA (Figure 5B), and was associated with an increase in apoptosis (Figure 5C). The apoptosis level induced by control siRNA transfection alone (9.6±1.3% compared with 18.5±1.6%, P<0.05) was enhanced further with individual KL-directed siRNAs (siRNA2: 29.1±2.5%, P<0.05 compared with control siRNA; Figure 5C). In addition, the mRNA expression of inflammatory cytokines [IL-6, MCP-1 (monocyte chemoattractant protein 1) and IL-8] was significantly upregulated by KL knockdown (Figure 5D). However, no effect on protein secretion was observed (results not shown).
Affiliation: Department of Respiratory Medicine, The First Affiliated Hospital of Nanjing Medical University, 300 Guangzhou Road, Nanjing 210029, China.