MITOCHONDRIA AT THE CROSSROADS BETWEEN LI FE AND DEATH - THE ROLE OF HEAT-SHOCK PROTEINS AND EFFECTS ON INFLAMMATION

As molecular chaperones, stress/heat shock proteins (HSP) play a criti cal role in cell biology and survival under stress conditions. Inducti on of HSP (Hsp70 and Hsp27 in particular), following either a thermal pretreat-ment or overexpression of the corresponding genes, leads to a general tolerance to cellular stresses: thermotolerance, protection a gainst oxidative lesions such as post-ischemic cell damage, TNF alpha cytoxicity, and to the inhibition of associated apoptotic processes On the one hand, mitochondria are involved in the decision process as to whether a cell will survive or die, and whether it will do so by necr osis or by apoptosis the other hand, the maintenance mitochondrial fun ctional integrity is a prefered target for protection by Hsp70. Hsp70 therefore participates, at the mitochondrial level, in the control of the <<choice>> of cell death,probably in cooperation with Hsp27, the l atter determining glutathione levels. These phenomena play essential r oles in inflammatory processes, inasmuch the type of cell death determ ines the outcome of inflammation. Indeed. inflammation is amplified ce ll necrosis, while apoptosis can limit it. However, one has io take in to account the potential risk of the antiapoptotic effect of HSP. Unle ss finely tuned, it could, in the end, contribute to chronic inflammat ion. Asthma, as a chronic inflammatory-disease of the upper airways, m ay be considered as a model pathology to illustrate these concepts.