title: IKK-β-mediated myeloid cell activation exacerbates inflammation and inhibits recovery after spinal cord injury.
abstract: Traumatic spinal cord injury (SCI) is followed by massive infiltration and activation of myeloid cells such as neutrophils and macrophages, but the functions of these cells are controversial. In this study, our objective was to elucidate the in vivo role of a signaling pathway involved in activation of these innate immune cells in SCI using myeloid cell-specific IκB kinase (IKK)-β conditional knockout (ikkβΔmye) mice. In these mice, the ikkβ gene has been specifically deleted from myeloid cells, compromising their in vivo IKK/NF-κB-dependent activation. We found that ikkβΔmye mice had significantly reduced neutrophil and macrophage infiltrations after SCI compared to ikkβ(+/+) controls. SCI-induced proinflammatory gene expression was also reduced in ikkβΔmye mice. Reduced neuroinflammation in ikkβΔmye mice was accompanied by attenuated neuronal loss and behavioral deficits in motor activity. In addition, the SCI-induced expression of CXC ligand 1 was reduced in ikkβΔmye mice, which may be responsible for the reduced neutrophil infiltration in these mice. Our data demonstrate that IKK-β-dependent myeloid cell activation potentiates neuroinflammation and neuronal damage after SCI.
authors.affiliation: Department of Neuroscience, School of Dentistry and Dental Research Institute, Brain Korea, Seoul National University, Seoul, Korea.
authors.forename: Junghee
authors.initials: J
authors.lastname: Kang
authors.forename: Mei Hua
authors.initials: MH
authors.lastname: Jiang
authors.forename: Hyun Jung
authors.initials: HJ
authors.lastname: Min
authors.forename: Eun-Kyeong
authors.initials: EK
authors.lastname: Jo
authors.forename: Soojin
authors.initials: S
authors.lastname: Lee
authors.forename: Michael
authors.initials: M
authors.lastname: Karin
authors.forename: Tae Young
authors.initials: TY
authors.lastname: Yune
authors.forename: Sung Joong
authors.initials: SJ
authors.lastname: Lee
mesh_terms: D000818:Animals; D017209:Apoptosis; D016923:Cell Death; D054360:Chemokine CXCL1 / Q000235:genetics / Q000378:metabolism; D004797:Enzyme-Linked Immunosorbent Assay; D005434:Flow Cytometry; D015870:Gene Expression; D005786:Gene Expression Regulation; D051550:I-kappa B Kinase / Q000235:genetics / Q000378:metabolism*; D020287:In Situ Nick-End Labeling; D007249:Inflammation / Q000235:genetics / Q000276:immunology; D008262:Macrophage Activation; D008264:Macrophages / Q000276:immunology* / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D016328:NF-kappa B / Q000276:immunology / Q000378:metabolism; D009474:Neurons / Q000473:pathology; D020556:Neutrophil Infiltration; D009504:Neutrophils / Q000276:immunology* / Q000378:metabolism; D016133:Polymerase Chain Reaction; D026361:Reactive Nitrogen Species / Q000378:metabolism; D017382:Reactive Oxygen Species / Q000378:metabolism; D015398:Signal Transduction; D013116:Spinal Cord; D013119:Spinal Cord Injuries / Q000235:genetics / Q000276:immunology* / Q000378:metabolism / Q000473:pathology
chemical_list: D054360:Chemokine CXCL1; C475895:Cxcl1 protein, mouse; D016328:NF-kappa B; D026361:Reactive Nitrogen Species; D017382:Reactive Oxygen Species; D051550:I-kappa B Kinase; C496562:Ikbkb protein, mouse