title: Apolipoprotein E isoform-specific effects on cytokine and nitric oxide production from mouse Schwann cells after inflammatory stimulation.
abstract: Previously, we reported that apolipoprotein E (apoE) deficiency increased the susceptibility to experimental autoimmune neuritis (EAN), an inflammatory autoimmune disorder of the peripheral nervous system (PNS) and an animal model for human Guillain-Barré syndrome (GBS) by affecting the antigen-presenting function of Schwann cells (SCs) via influence upon IL-6 production. To further elucidate the role of apoE in inflammation of the PNS, here we studied the effect of different isoforms of apoE on SCs in response to inflammatory stimulation. SCs from apoE2, E3 and E4 transgenic (Tg) and wild type (WT) mice were cultured, and their responses to stimulation by lipopolysaccharide (LPS) plus interferon (IFN)-γ were compared. Upon stimulation, the morphology of cultured SCs changed. Pronounced production of interleukin (IL)-6 and IL-10 within SCs, and of IL-6 and nitric oxide (NO) in the supernatants were found in an isoform-dependent manner (apoE3>apoE2≈apoE4). Further results indicated that both nuclear factor (NF) κB and Akt signaling pathways were involved in the process by the same isoform-dependent pattern. However, the expression of co-stimulatory molecules as showing the antigen-presenting capacity of SCs was not significantly different among these groups. In conclusion, SCs respond to inflammatory insults accompanied by increased productions of IL-6, IL-10 and NO in an apoE-isoform-dependent manner. SCs from apoE2 and apoE4 Tg mice seem to bear some dysfunction in producing cytokines (IL-6 and IL-10) and NO as compared with their apoE3 counterparts, probably resulting from their insufficiency to suppress the activation of NFκB and Akt pathways. Our findings may help to understand the role of different isoforms of apoE in inflammatory disorders of the PNS.
authors.affiliation: Department of Plastic Surgery, the First Hospital of Jilin University, Changchun, China.
authors.forename: Ke-Jia
authors.initials: KJ
authors.lastname: Zhang
authors.forename: Hong-Liang
authors.initials: HL
authors.lastname: Zhang
authors.forename: Xing-Mei
authors.initials: XM
authors.lastname: Zhang
authors.forename: Xiang-Yu
authors.initials: XY
authors.lastname: Zheng
authors.forename: Hernan Concha
authors.initials: HC
authors.lastname: Quezada
authors.forename: Duo
authors.initials: D
authors.lastname: Zhang
authors.forename: Jie
authors.initials: J
authors.lastname: Zhu
mesh_terms: D000818:Animals; D053329:Apolipoprotein E2 / Q000235:genetics; D053318:Apolipoprotein E3 / Q000235:genetics*; D053327:Apolipoprotein E4 / Q000235:genetics*; D018929:Cell Culture Techniques; D007371:Interferon-gamma / Q000494:pharmacology; D016753:Interleukin-10 / Q000378:metabolism*; D015850:Interleukin-6 / Q000378:metabolism*; D008070:Lipopolysaccharides / Q000494:pharmacology; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D016328:NF-kappa B / Q000378:metabolism; D009569:Nitric Oxide / Q000378:metabolism*; D020033:Protein Isoforms / Q000235:genetics*; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism; D012583:Schwann Cells / Q000187:drug effects / Q000378:metabolism*; D015398:Signal Transduction / Q000187:drug effects
chemical_list: D053329:Apolipoprotein E2; D053318:Apolipoprotein E3; D053327:Apolipoprotein E4; D015850:Interleukin-6; D008070:Lipopolysaccharides; D016328:NF-kappa B; D020033:Protein Isoforms; D016753:Interleukin-10; D009569:Nitric Oxide; D007371:Interferon-gamma; D051057:Proto-Oncogene Proteins c-akt