INDUCTION OF HEAT-SHOCK PROTEIN IN MONOCYTIC CELLS BY OXIDIZED LOW-DENSITY-LIPOPROTEIN

The atherosclerotic lesion may be characterized as a chronic inflammat ory process, and oxidized LDL is believed to be a key event in the dev elopment of atherosclerosis, though the mechanisms by which oxidized L DL exerts its proatherogenic properties are largely unknown. Heat shoc k proteins (hsp) are a group of proteins with a highly conserved struc ture and of these, hsp60 has been suggested to play a role in autoimmu nity due to T lymphocyte crossreactivity between bacterial and human h sp60. The present study was designed to investigate the effects of oxi dized LDL on the expression of hsp60 using the monocytic cell lines U9 37 and HL60 as models. The expression of hsp60 was determined by using monoclonal antibodies to hsp60 in FACScan, Western blot, and a sandwi ch ELISA. The results show that hsp60 is induced in both cell types af ter 2 h exposure to oxidized LDL, with a maximal effect at 20 mu g/ml for U937 cells and 5 mu g/ml for HL60 cells. A close to 3-fold increas e in the expression of hsp60 was seen after culturing oxidized LDL (20 mu g/ml) treated U937 cells for a period of 24 h. Interleukin 1-beta had similar effects on hsp60 expression to oxidized LDL. The results i ndicate that expression of hsp60 by monocytes in the vascular wall may be enhanced by oxidized LDL. It is thus possible that the chronic inf lammatory process characterizing atherosclerosis is perpetuated by aut oreactive T cells, which recognize hsp60 expressed by monocytes, induc ed by oxidized LDL.