title: N9 microglial cells polarized by LPS and IL4 show differential responses to secondary environmental stimuli.
abstract: Microglia participates in the regulation of many inflammation-related pathological processes in the central nervous system, but how microglial activation is regulated has not been fully understood. Here, by using a microglial cell line, we show that microglia, like other macrophages, are activated by inflammatory stimuli in a polarized manner. The LPS-polarized M1 microglia appeared to be unable to respond to a secondary IL4 stimulation, while IL4-polarized M2 microglia could respond to secondary LPS stimulation. We also show that Notch signaling is involved in microglial polarization. When Notch signaling was blocked, the M1 polarization was suppressed, while the M2 polarization was promoted. Withdraw of the Notch signal inhibitor did not permit M2 N9 cells to re-polarize to M1 upon LPS stimulation, suggesting that the effects of Notch blockade on microglial polarization could be "memorized" by cells. These results suggest complicated mechanisms including epigenetic programs in the regulation of macrophage polarization.
authors.affiliation: State Key Laboratory of Cancer Biology, Department of Medical Genetics and Developmental Biology, Fourth Military Medical University, Xi'an, China.
authors.forename: Hong-Cui
authors.initials: HC
authors.lastname: Liu
authors.forename: Min-Hua
authors.initials: MH
authors.lastname: Zheng
authors.forename: Yan-Ling
authors.initials: YL
authors.lastname: Du
authors.forename: Li
authors.initials: L
authors.lastname: Wang
authors.forename: Fang
authors.initials: F
authors.lastname: Kuang
authors.forename: Hong-Yan
authors.initials: HY
authors.lastname: Qin
authors.forename: Bing-Fang
authors.initials: BF
authors.lastname: Zhang
authors.forename: Hua
authors.initials: H
authors.lastname: Han
mesh_terms: D053829:Amyloid Precursor Protein Secretases / Q000037:antagonists & inhibitors; D000818:Animals; D002460:Cell Line; D044127:Epigenesis, Genetic; D015847:Interleukin-4 / Q000494:pharmacology*; D008070:Lipopolysaccharides / Q000494:pharmacology*; D051379:Mice; D017628:Microglia / Q000166:cytology / Q000187:drug effects* / Q000276:immunology; D009569:Nitric Oxide / Q000096:biosynthesis / Q000276:immunology; D051880:Receptors, Notch / Q000037:antagonists & inhibitors / Q000235:genetics / Q000276:immunology*; D015398:Signal Transduction
chemical_list: D008070:Lipopolysaccharides; D051880:Receptors, Notch; D015847:Interleukin-4; D009569:Nitric Oxide; D053829:Amyloid Precursor Protein Secretases