Background and Purpose-MIF has been implicated to function in many inflammatory processes. This study examined whether MIF expression was affected in stroke and its underlying molecular mechanism. Methods-ELISA and qRT-PCR were used to detect MIF protein and mRNA in PBMCs from stroke patients, the ischemic rat brains, and controls. A MIF promoter assay under hypoxia was performed. Results-MIF protein and mRNA were significantly increased in stroke patients. Increasing levels of MIF were correlated to the severity of stroke and peaked 24 hours after stroke. MIF was significantly upregulated in focal ischemic rat brains. The activity of the human MIF promoter was significantly increased under hypoxia compared to normoxia. Key Words: cell cultures Ⅲ gene regulation Ⅲ neurochemistry M acrophage migration inhibition factor (MIF) is a 12-kDa trimer protein consisting of 6 alpha helices and 3 beta sheets, which form a solvent channel through which negatively charged molecules may enter. 1 MIF is expressed by T cells, macrophages, monocytes, and endothelial cells. 2,3 MIF plays a prominent role in innate immunity and has been implicated in several inflammatory diseases including rheumatoid arthritis and pancreatitis as well as atherosclerosis. 4 -6 Strong MIF expression in macrophages has been shown to initiates and facilitates the atherogenesis process, 7 and MIF also affects ischemia-reperfusion injury in the heart. 8 However, the role of MIF in stroke has not be reported. Conclusions-MIFStroke is a debilitating disease that can cause severe neurological and motor deficits, resulting in long-term care and contributing significantly to health care costs. Neuronal death after an ischemic insult has been attributed to a variety of molecular processes. Studies showed that mice deficient in T lymphocytes have reduced tissue damage after experimental stroke, 9,10 and MIF is able to cause the arrest of circulating T cells and monocytes. 11 MIF expression was shown to be hypoxia-inducible. 12,13 Hypoxia is the major consequence of stroke. Although the effect of hypoxia on tissue viability has not been resolved, we showed that hypoxia facilitates Alzheimer disease pathogenesis. 14 In this report we investigated MIF gene expression in human stroke patients and stroke model rats. Our data demonstrate that MIF is upregulated under stroke, and hypoxia facilitates the transcription of MIF gene. Materials and Methods Human SubjectsThe criteria for patient selection were followed according to the Fourth Chinese National Meeting for Cerebrovascular Disease (1996). Incidence of stroke was confirmed by head CT scan or MRI. The study included 102 patients (61 males and 41 females with an average age of 68.61Ϯ9.64) and 57 controls (32 males and 25 females with an average age of 68.12Ϯ10.84; PϾ0.05). There was also no significant difference in subjects having a history of hypertension, diabetes mellitus, drinking, and smoking between the two groups (PϾ0.05). The stroke patients had significantly higher levels of blood pressure, triglyce...

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