title: Sex steroid hormone-mediated functional regulation of microglia-like BV-2 cells during hypoxia.
abstract: 17β-estradiol (E2) and progesterone (P) are neuroprotective hormones in different neurological disorders and in particular under hypoxic conditions in the brain. Both hormones dampen brain-intrinsic immune responses and regulate local glial cell function. Besides astrocytes which are functionally regulated in a manifold and complex manner, especially microglial cells are in the focus of steroid-mediated neuroprotection. In previous studies using a transient brain artery occlusion model, we demonstrated that microglial characteristics are critically modified after the administration of either E2 or P. We here studied the influence of sex steroids on the murine BV-2 microglia cell line under hypoxic conditions. Hypoxia changed the cell morphology from an amoeboid-like phenotype with processes to a rounded shape of secreting cell type. BV-2 cells expressed both estrogen receptor-β and progesterone receptors under each condition. Oxygen deprivation increased the expression of inducible nitric oxide synthetase (iNOS) and up-regulated selected cytokines and chemokines. Both hormones selectively prevented the induction of pro-inflammatory iNOS, interleukin IL-1ß, and chemokine ligand CCL5, whereas anti-inflammatory IL-10 and protective TREM 2 were up-regulated by sex steroids. Sex hormones abrogated hypoxia-dependent reduction of BV-2 phagocytic activity. We demonstrate that BV-2 microglia cells respond to hypoxia by enhanced pro-inflammatory cytokine secretion and reduced phagocytic activity. This effect is prevented by sex steroids resulting in a switch of BV-2 cells from a pro-inflammatory to a more anti-inflammatory phenotype. Anti-inflammatory effects of gonadal steroids might directly be mediated through hormone-microglia interactions in addition to known effects via astroglial regulation.
authors.affiliation: Institute of Neuroanatomy, RWTH Aachen University, 52074 Aachen, Germany.
authors.forename: Pardes
authors.initials: P
authors.lastname: Habib
authors.forename: Daniela
authors.initials: D
authors.lastname: Dreymueller
authors.forename: Andreas
authors.initials: A
authors.lastname: Ludwig
authors.forename: Cordian
authors.initials: C
authors.lastname: Beyer
authors.forename: Jon
authors.initials: J
authors.lastname: Dang
mesh_terms: D000818:Animals; D015687:Cell Hypoxia / Q000187:drug effects*; D018946:Chemokine CCL5 / Q000378:metabolism; D018925:Chemokines / Q000378:metabolism; D016207:Cytokines / Q000378:metabolism; D012739:Gonadal Steroid Hormones / Q000494:pharmacology*; D016753:Interleukin-10 / Q000378:metabolism; D053583:Interleukin-1beta / Q000378:metabolism; D051379:Mice; D017628:Microglia / Q000187:drug effects / Q000378:metabolism*; D052247:Nitric Oxide Synthase Type II / Q000378:metabolism
chemical_list: D018946:Chemokine CCL5; D018925:Chemokines; D016207:Cytokines; D012739:Gonadal Steroid Hormones; D053583:Interleukin-1beta; D016753:Interleukin-10; D052247:Nitric Oxide Synthase Type II
keywords: BV2; Estrogen; Hypoxia; Microglia; Neuroinflammation; Progesterone