Inflammation stimulates thrombopoietin (Tpo) expression in rat brain-derived microvascular endothelial cells, but suppresses Tpo in astrocytes and microglia.
Thrombopoietin (Tpo) and its receptor (c-Mpl; TpoR), which primary regulate megakaryopoiesis and platelet production, are also expressed in the central nervous system (CNS). Increased Tpo concentrations are present in the cerebrospinal fluid (CSF) of some patients with bacterial or viral meningitis. Since previous data implicated a proapoptotic role of Tpo on newly generated neuronal cells, we herein elucidated the regulation of Tpo in primary rat neurons (e17), astrocytes, and microglia (p0-p3), as well as in brain-derived vascular endothelial cells of 3-week-old rats after exposure to bacterial lipopolysaccharide (LPS). LPS inhibited Tpo gene expression in astrocytes and microglia, but not in neurons, most likely due to absence of Toll-like receptor 4 in neurons. While Tpo mRNA expression recovered in astrocytes after 24 h, it remained suppressed in microglia. Furthermore, we detected Tpo mRNA expression in primary brain-derived vascular endothelial cells, which also express the TpoR. In these cells, LPS significantly up-regulated Tpo mRNA expression. TpoR mRNA and protein expression remained constitutive in all cell types. Thus, our data provide evidence for a cell-type-specific modulation of Tpo mRNA expression by inflammation in brain-derived cells. Transient down-regulation of Tpo expression in astrocytes and microglia may limit Tpo-induced neuronal cell death in inflammatory brain disorders.
Department of Neonatology, Charité-Universitätsmedizin Berlin, Berlin, Germany.
Juan
J
Zhang
Dorette
D
Freyer
Olga
O
Rung
Ae-Rie
AR
Im
Olaf
O
Hoffmann
Christof
C
Dame
D000818:Animals; D000831:Animals, Newborn; D001253:Astrocytes / Q000276:immunology / Q000378:metabolism* / Q000473:pathology; D002478:Cells, Cultured; D015536:Down-Regulation; D004622:Embryo, Mammalian; D004730:Endothelium, Vascular / Q000276:immunology / Q000378:metabolism* / Q000473:pathology; D007249:Inflammation; D008070:Lipopolysaccharides / Q000276:immunology / Q000378:metabolism; D017628:Microglia / Q000276:immunology / Q000378:metabolism* / Q000473:pathology; D051381:Rats; D017208:Rats, Wistar; D053628:Receptors, Thrombopoietin / Q000096:biosynthesis* / Q000235:genetics / Q000276:immunology; D013926:Thrombopoietin / Q000096:biosynthesis* / Q000235:genetics / Q000276:immunology; D015854:Up-Regulation
D008070:Lipopolysaccharides; D053628:Receptors, Thrombopoietin; D013926:Thrombopoietin