Hypoxia-reoxygenation-induced chemokine transcription is not prevented by preconditioning or intermittent hypoxia, in mice hepatocytes

In liver surgery and/or transplantation, prolonged ischemia is necessary to avoid excessive blood loss. Partial oxygen pressure (PO2) variation is one of the most important damaging factors playing a part in ischemia– reperfusion (I/R) injuries. Its decrease during vascular clamp, and its abrupt increase during organ reperfusion, cause functional and structural damage to liver cells, resulting in apoptosis [1] and necrosis [2] which may occur in parallel. Both processes contribute to cell death and liver dysfunction, which represent an important cause of morbidity and mortality [1]. It is well known that the neutrophil plays an important role in the development of I/R-induced necrosis [3]. Hepatic injury following I/R consists of two periods: (i) the initial phase (1–6-h postreperfusion) is associated with oxygen-free radical generation [1], Kupffer cell activation, and initial release of neutrophils [3]. Several studies, especially in in vivo models have shown that I/R led to pro-inflammatory cytokine secretion [tumor necrosis factor (TNF)-a, interleukin-1 (IL-1)] by Kupffer cells [4,5]. In response to this cytokine secretion, hepatocytes release chemokines, which have neutrophil chemotactic properties (CXC chemokines) [6,7]. Chemokines are a family of leukocyte chemoattractant proteins which are