Paclitaxel protected against lipopolysaccharide (LPS)-induced acute kidney injury and improved animal survival. In cultured renal tubular HK-2 cells, paclitaxel decreased the DNA binding activity of nuclear factor-κB (NF-κB) during LPS treatment, inhibited the degradation of IκBa, and blocked the expression and activation of NF-κB-p65. In an in vitro assay, paclitaxel was shown to directly bind recombinant myeloid differentiation protein-2 (MD-2), and the inhibitory effect on NF-κB activation and cytokine expression disappeared in MD-2 knockdown cells. Collectively, these results suggest that paclitaxel bind MD-2 to block MD-2/Toll-like receptor 4 association during LPS treatment, resulting in the suppression of NF-κB activation and inhibition of proinflammatory cytokine production.
See article at J Pharmacol Exp Ther 2013, 345:69–75.
- Copyright © 2013 by The American Society for Pharmacology and Experimental Therapeutics