Leukaemia inhibitory factor is over-expressed by ischaemic brain tissue concomitant with reduced plasma expression following acute stroke.
Leukaemia inhibitory factor (LIF) is a glycoprotein of the interleukin-6 family, which has potent pro-inflammatory properties and is involved in regulation of neuronal differentiation. We have previously identified its upregulation in gene microarrays following acute ischaemic stroke in man. LIF expression and localization was measured in human ischaemic stroke autopsy specimens, in a rat model of middle cerebral artery occlusion (MCAO) and in human foetal neural cell cultures following oxygen-glucose deprivation (OGD) by Western blotting and immunohistochemistry. Circulating LIF was determined in the plasma of patients in the hyper-acute stroke phase using a multiplex enzyme-linked-immunosorbent serologic assay system. Patients demonstrated an increase in LIF expression in peri-infarcted regions with localization in neurons and endothelial cells of microvessels surrounding the infarcted core. The rat MCAO model showed similar upregulation in neurons with a peak increase at 90 min. Circulating serum LIF expression was significantly decreased in the hyper-acute phase of stroke. Brain-derived neurons and glia cultured in vitro demonstrated an increase in gene/protein and protein expression respectively following exposure to OGD. Increased LIF expression in peri-infarcted regions and sequestration from the peripheral circulation in acute stroke patients are characteristic of the pathobiological response to ischaemia and tissue damage.
The Department of Biology, Chemistry and Health Science, Manchester Metropolitan University, Manchester, UK. m.a.slevin@mmu.ac.uk
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Slevin
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Krupinski
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Mitsios
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Perikleous
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Cuadrado
J
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Montaner
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Sanfeliu
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Luque
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Kumar
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Kumar
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Gaffney
D000208:Acute Disease; D000368:Aged; D000369:Aged, 80 and over; D000818:Animals; D001921:Brain / Q000098:blood supply / Q000378:metabolism* / Q000503:physiopathology; D002545:Brain Ischemia / Q000097:blood* / Q000503:physiopathology*; D002478:Cells, Cultured; D018920:Coculture Techniques; D004195:Disease Models, Animal; D018450:Disease Progression; D042783:Endothelial Cells; D005260:Female; D006801:Humans; D020244:Infarction, Middle Cerebral Artery / Q000097:blood / Q000503:physiopathology; D053605:Leukemia Inhibitory Factor / Q000096:biosynthesis / Q000097:blood* / Q000235:genetics; D008297:Male; D008875:Middle Aged; D009457:Neuroglia / Q000378:metabolism; D009474:Neurons / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D020521:Stroke / Q000097:blood* / Q000503:physiopathology*; D015854:Up-Regulation / Q000502:physiology
D053605:Leukemia Inhibitory Factor