The remote ischemic preconditioning stimulus modifies inflammatory gene expression in humans

Physiological Genomics - Tập 19 Số 1 - Trang 143-150 - 2004
Igor E. Konstantinov1, Sara Arab2, Rajesh Kharbanda3, Jia Li4, Michael M.H. Cheung4, Vera Cherepanov5, Gregory P. Downey5, Peter P. Liu2, Eva Cukerman2, John G. Coles1, Andrew N. Redington4
1Division of Cardiovascular Surgery, Hospital for Sick Children/University of Toronto, Toronto, Canada
2Division of Cardiology, Heart and Stroke/Richard Lewar Centre of Excellence, University of Toronto, Toronto, Canada
3University of Cambridge, Addenbrooke’s Centre for Clinical Investigation, Cambridge, United Kingdom
4Division of Cardiology, Hospital for Sick Children, University of Toronto, Toronto, Canada
5Division of Respirology, Toronto General Hospital, University of Toronto, Toronto, Canada

Tóm tắt

Remote ischemic preconditioning (IPC) reduces tissue injury caused by ischemia-reperfusion (IR) in distant organs. We tested the hypothesis that remote IPC (rIPC) modifies inflammatory gene transcription in humans. Using a microarray method, we demonstrated that a simple model of brief forearm ischemia suppresses proinflammatory gene expression in circulating leukocytes. Genes encoding key proteins involved in cytokine synthesis, leukocyte chemotaxis, adhesion and migration, exocytosis, innate immunity signaling pathways, and apoptosis were all suppressed within 15 min (early phase IPC) and more so after 24 h (second window IPC). Changes in leukocyte CD11b expression measured by flow cytometry mirrored this pattern, with there being a significant ( P = 0.01) reduction at 24 h. The results of this study show that the rIPC stimulus modifies leukocyte inflammatory gene expression. This effect may contribute to the protective effect of IPC against IR injury and may have broader implications in other inflammatory processes. This is the first study of human gene expression following rIPC stimulus. rIPC stimulus suppressed proinflammatory gene transcription in human leukocytes.

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