A mechanism converting psychosocial stress into mononuclear cell activation

Proc. Natl. Acad. Sci. USA. 2003;100: p1920-1925.

Speaker: 林長儀

Time: 92/12/31 15:00~16:00        

Commentator: 余俊強 老師

Place: Room 601

Abstract:

Long-term psychosocial stress such as depression, anxiety, personality factors, social isolation, and chronic life stress would lead to increase the risk of cardiovascular diseases¹. However, psychosocial stress triggers releasing not only stress hormone like ACTH, cortisol, catecholamines [adrenalin(AD), noradrenalin(NA)], but also inflammatory cytokines from activated peripheral blood mononuclear cell (PBMC). Previous study indicated that β-adrenergic receptor blockade significantly inhibited the stress effect on cardiovascular diseases. But stress mediated signal pathway is still unkown. In atherosclerosis, the activation of NF-κB was found in smooth muscle cells, macrophages, and endothelial cells². In this study, the authors tried to 1.) demonstrate that whether psychosocial stress would activate PBMC through NF-κB activation and 2.) define the cellular signals cascades. The results show that stress exposure increases rapidly not only the level of stress hormone but also NF-κB binding activity of PBMC. In animal models, immobilization stress also can activate NF-κB and which could be inhibited by α1-adrenergic inhibitor, prazosin. To investigate the role of catecholamine, the authors find that NA, but not AD, can increase NF-κB binding activity and IL-6 expression in THP-1 cells. Furthermore, the authors demonstrate the signal cascades by utilizing specific inhibitors of signaling transduction. Results show the signal pathway involving adrenergic receptor, Ptx-sensitive G proteins, PI3-kinase, Ras/Raf, and MAPK activation. The data provide a strong evidence for psychosocial stress converting into mononuclear cell activation. This might open a window to a more profound understanding of the mechanisms linking stress and disease.

Reference:

1.            Rozanski. A., J. A. Blumenthal and J. Kaplan. 2000. Impact of Psychological Factors on the Pathogenesis of Cardiovascular Disease and Implications for Therapy. Circulation. 99, 2192-2217.

2.          Collins, T., and M. I. Cybulsky. 2001.NF-κB: pivotal mediator or innocent bystander in atherogenesis? J. Clin. Invest. 107, 255-264.

3.          Bierhaus, A., et al. 2003. A mechanism converting psychosocial stress into mononuclear cell activation. Proc. Natl. Acad. Sci. USA. 100, 1920-1925.