The remote ischemic preconditioning stimulus modifies inflammatory gene expression in humans.
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.
Division of Cardiovascular Surgery, Hospital for Sick Children, University of Toronto, Toronto, ON, Canada.
Igor E
IE
Konstantinov
Sara
S
Arab
Rajesh K
RK
Kharbanda
Jia
J
Li
Michael M H
MM
Cheung
Vera
V
Cherepanov
Gregory P
GP
Downey
Peter P
PP
Liu
Eva
E
Cukerman
John G
JG
Coles
Andrew N
AN
Redington
D000328:Adult; D039481:CD11b Antigen / Q000235:genetics; D005260:Female; D005434:Flow Cytometry; D005786:Gene Expression Regulation / Q000235:genetics*; D006801:Humans; D007249:Inflammation / Q000235:genetics* / Q000276:immunology / Q000473:pathology; D019194:Ischemic Preconditioning; D007962:Leukocytes / Q000276:immunology / Q000378:metabolism; D008297:Male; D018375:Neutrophil Activation; D020411:Oligonucleotide Array Sequence Analysis; D012333:RNA, Messenger / Q000032:analysis / Q000235:genetics; D015427:Reperfusion Injury / Q000235:genetics / Q000473:pathology / Q000517:prevention & control; D015203:Reproducibility of Results
D039481:CD11b Antigen; D012333:RNA, Messenger