Albumin activates astrocytes and microglia through mitogen-activated protein kinase pathways.
Following acute brain injury, albumin may gain access to the brain parenchyma. Clinical studies indicate a protective role for albumin in stroke but an increase in mortality associated with albumin administration following traumatic brain injury. We investigated the effects of albumin on astrocyte and microglial activation, and the role of mitogen-activated protein kinases (MAPK) in these responses. Albumin activated ERK1/2, p38 MAPK and JNK signaling pathways in astrocytes, and induced the production of interleukin (IL)-1beta, inducible nitric oxide (NO) synthase, the NO metabolite nitrite, and the chemokine CX3CL1 while reducing the level of S100B. The release of inflammatory markers by astrocytes was partially dependent on p38 MAPK and ERK1/2 pathways, but not JNK. In microglia, albumin exposure activated all three MAPK pathways and produced an increase in IL-1beta and nitrite. Inhibition of p38 MAPK in microglia leads to an increased level of IL1beta, while inhibition of all three MAPKs suppressed the release of nitrite. These results suggest that albumin activates astrocytes and microglia, inducing inflammatory responses involved both in the mechanisms of cellular injury and repair via activation of MAPK pathways, and thereby implicate glial activation in the clinical responses to administration of albumin.
Ralay Ranaivo
Hantamalala
H
Department of Pediatrics, Division of Neurology, Northwestern University Feinberg School of Medicine, Chicago, IL, USA.
Wainwright
Mark S
MS
D000418:Albumins / Q000378:metabolism*; D000818:Animals; D001253:Astrocytes / Q000502:physiology*; D002470:Cell Survival / Q000502:physiology; D002478:Cells, Cultured; D002540:Cerebral Cortex / Q000502:physiology; D054428:Chemokine CX3CL1 / Q000378:metabolism; D048049:Extracellular Signal-Regulated MAP Kinases / Q000378:metabolism; D053583:Interleukin-1beta / Q000378:metabolism; D020935:MAP Kinase Signaling System / Q000502:physiology*; D017628:Microglia / Q000502:physiology*; D020928:Mitogen-Activated Protein Kinases / Q000037:antagonists & inhibitors / Q000378:metabolism*; D009414:Nerve Growth Factors / Q000378:metabolism; D009573:Nitrites / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D064568:S100 Calcium Binding Protein beta Subunit; D009418:S100 Proteins / Q000378:metabolism; D048051:p38 Mitogen-Activated Protein Kinases / Q000378:metabolism
D000418:Albumins; D054428:Chemokine CX3CL1; C515540:Cx3cl1 protein, rat; D053583:Interleukin-1beta; D009414:Nerve Growth Factors; D009573:Nitrites; D064568:S100 Calcium Binding Protein beta Subunit; D009418:S100 Proteins; C579158:S100b protein, rat; D048049:Extracellular Signal-Regulated MAP Kinases; D020928:Mitogen-Activated Protein Kinases; D048051:p38 Mitogen-Activated Protein Kinases