Antibody treatment, however, lessened fractional excretion of phosphate, thus increasing serum phosphate levels, and normalized serum 1,25-dihydroxyvitamin D by increased 1 alpha-OHase and decreased 24-OHase expressions in the kidney. These antibody-induced changes
were followed by increased serum calcium levels, leading to decreased serum parathyroid hormone. Hence, our study shows that FGF23 normalizes serum phosphate and decreases 1,25-dihydroxyvitamin D levels in early-stage CKD, and suggests a pathological sequence of events for the development of secondary hyperparathyroidism triggered by increased FGF23, followed by a reduction of 1,25-dihydroxyvitamin D and calcium levels, thereby increasing parathyroid hormone secretion.”
“Ethyl pyruvate (EP) is a stable derivative of pyruvate and has been identified as a therapeutic agent for various inflammatory diseases. In the present study, we showed that EP and sodium pyruvate click here (SP) inhibited the production of TNF-alpha, nitric oxide MK-4827 nmr (NO), or reactive oxygen species (ROS) in LPS-stimulated BV2 microglial cells. The inhibitory effects of EP were more potent than SP. Because matrix metalloproteinase-9 (MMP-9) plays a key role in neuroinflammation, as well as
in neuronal cell death, we examined the effect of EP on MMP-9 expression. RT-PCR and Western blot analyses revealed that EP inhibits MMP-9 expression at mRNA and protein levels in LPS-stimulated BV2 cells. In addition, EP suppressed MMP-9 secretion, as demonstrated by gelatin zymography analysis. In contrast, SP did not affect MMP-9 expression at an equivalent concentration of EP. Further mechanistic studies revealed that EP inhibits MMP-9 promoter activity by reducing the binding of NF-kappa B and AP-1 to its cognitive binding sites. In addition, EP suppressed LPS-induced phosphorylation of p38 MAPK, ERK, and Akt, which are upstream
DCLK1 signaling molecules in MMP-9 gene expression. Taken together, our data suggest that the inhibition of MMP-9 may be one of the factors contributing to anti-inflammatory activity of EP in LPS-stimulated microglia. (C) 2011 Elsevier Ireland Ltd. All rights reserved.”
“Dendritic cells have the potential to induce tolerance and here we attempted to identify their role in the tolerance seen in ischemic pre-conditioning. We induced bilateral renal ischemic preconditioning in mice and then challenged them with an ischemic insult 7 days later. Compared to sham-operated controls, preconditioned mice were found to have reduced injury with less inflammation, but had an increased number of regulatory T cells (Tregs) in their kidneys after the delayed insult. Splenocytes from these mice had more Tregs and mature CD11c(+) cells, but reduced proliferative and cytokine-secretory responses, suggesting a state of immunosuppression compared to control mice.