International journal of molecular medicine
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Mitochondrial DNA (mtDNA) contains unmethylated CpG motifs that exhibit immune stimulatory capacities. The aim of this study was to investigate whether mtDNA activates the Toll-like receptor 9 (TLR9)/nuclear factor-κB (NF-κB) pathway, thereby contributing to post-traumatic systemic inflammatory response syndrome (SIRS) and lung injury in rats. The effects of mtDNA on macrophage culture were examined in order to elucidate the putative cellular mechanisms. ⋯ In addition, mtDNA increased serum tumor necrosis factor-α, interleukin (IL)-6 and IL-10 levels in vivo and increased their secretion by cultured macrophages (p<0.05). In lung tissue, mtDNA increased NF-κB, IκB-α and TLR9 mRNA levels (p<0.05); it also increased phosphorylated NF-κB p65 and TLR9 protein levels in the macrophage cultures. Thus, mtDNA may be part of the danger-associated molecular patterns, contributing to the initiation of sterile SIRS through the activation of the TLR9/NF-κB pathway and the induction of pro-inflammatory cytokine production.
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Podocytes are terminally differentiated epithelial cells lacking the ability to proliferate. The loss of podocytes is a hallmark of progressive kidney diseases, including diabetic nephropathy (DN). Endoplasmic reticulum stress (ERS)-induced apoptosis is involved in a number of pathological conditions, including DN. ⋯ CHOP/GADD153 expression reached its peak at 48 h, and caspase-12 expression gradually increased with time. Spearman's correlation analysis revealed that caspase-12 and CHOP/GADD153 positively correlated with the apoptotic rate (r=0.915, P<0.01 and r=0.639, P<0.01). Our results demonstrated that hyperglycemia (high glucose) induced apoptosis partly through ERS in the differentiated mouse podocytes, which possibly contributes to the pathogenesis of DN.