GLUCOSE-REGULATED PROTEIN 78 PROMPTS SCAVENGER RECEPTOR A-MEDIATED SECRETION OF TUMOUR NECROSIS FACTOR-alpha BY RAW 264.7 CELLS

摘要

1. Activation of macrophages plays an important role in atherosclerosis. In order to investigate the effect of endoplasmic reticulum (ER) stress on cytokine release from macrophages, the RAW 264.7 mouse macrophage cell line was treated with 0.2 mmol/L 6-aminonicotinamide (6-AN) for 36 h and the secretion of tumour necrosis factor (TNF)-a determined. In addition, Raw 264.7 cells were incubated in the presence of 10 mug/mL acetylated low-density lipoprotein (acLDL) at 37degC for 8 h.2. Secretion of TNF-alpha from RAW 264.7 cells was stimulated by both loading of cells with acLDL and following 6-AN treatment. In addition, the expression of glucose-regulated protein (GRP) 78 was increased in 6-AN-treated cells (by 165%).3. In separate experiments, PD98059, a specific inhibitor of the mitogen-activated protein kinase kinase (MEK) pathway, blocked acLDL- and/or 6-AN-induced TNF-a secretion, whereas LY294002, which blocks the AKT signalling pathway, had no effect. On the basis of these results, we speculate that acLDL/ 6-AN-induced secretion of TNF-alpha from RAW 264.7 cells may be regulated by activation of the MEK signalling pathway.4. The present study suggests that the accumulation of lipids in cells and/or ER stress could lead to macrophage apoptosis as a result of the increased production of TNF-a, which integrates into atherosclerosis.