Activation and regulation of Hsp32 and Hsp70

Endothelial cells (EC) play a key role in the propagation of inflammatory r esponses. Better understanding of inflammatory processes in EC might provid e new ways of controlling inflammation. We report here that the known antio xidant pyrrolidinedithiocarbamate (PDTC) leads to time and dose dependent a ctivation of heat-shock protein 70 (Hsp70) as well as Hsp32 in EC. We furth er demonstrate that PDTC activates heat-shock factor 1 (HSF1), one of sever al transcription factor involved in the upregulation of heat-shock proteins . And more importantly, we demonstrate that Hsp32 as well as Hsp70 can be u pregulated independently of the transcription factor nuclear factor kappaB (NF-kappa B). The presented data provide further insight into the mechanism of Hsp32 and Hsp70 regulation, as well as further distinguishing these gen es from other so called 'protective genes' whose upregulation depends on th e activation of NF-kappa B. These findings indicate that Hsp32 and Hsp70 mi ght be ideal candidates among protective genes. Hsp32 and Hsp70 provide man y desirable protective effects but, being independent of NF-kappa B, would leave open the option to interfere with the upregulation of proinflammatory genes by modulating the activation of NF-kappa B.