title: Blockade of IL-6 signaling by MR16-1 inhibits reduction of docosahexaenoic acid-containing phosphatidylcholine levels in a mouse model of spinal cord injury.
abstract: The interleukin (IL)-6 pathway plays an important role in recovery after spinal cord injury (SCI). The anti-IL-6 receptor antibody MR16-1 has been shown to suppress inflammation after SCI and promote recovery of motor function. The purpose of this study was to analyze the effects of MR16-1 on the expression patterns of phospholipids in the spinal cord in a mouse model of SCI. Eight-week-old C57BL/6JJmsSlc mice were used in this study. Laminectomy was performed at the ninth and tenth thoracic levels (T9-T10), and contusion injury of the spinal cord was induced at level T10. Immediately after SCI, mice were intraperitoneally injected with a single dose of MR16-1 (MR16-1 group) or a single dose of phosphate-buffered saline of the same volume (control group). Imaging mass spectrometry was performed to visualize phosphatidylcholine (PC) expression in the spinal cord 7 days after SCI. We found that MR16-1 treatment suppressed the infiltration of immune cells after SCI, and was able to increase the locomotor function post-injury. Phospholipid imaging revealed that the MR16-1 was able to prevent the reduction of docosahexaenoic acid (DHA)-containing PC in comparison with the control group. We also observed high levels of glial fibrillary acidic protein (GFAP) at the site of DHA-containing PC expression in the MR16-1 group. These results suggest that MR16-1 treatment influences the DHA-containing PC composition of GFAP-positive cells at the injury site as early as 7 days post-SCI.
authors.affiliation: Department of Orthopedic Surgery, Hamamatsu University School of Medicine, 1-20-1, Handayama, Higashi-ku, Hamamatsu, Shizuoka 431-3192, Japan.
authors.forename: H
authors.initials: H
authors.lastname: Arima
authors.affiliation: Department of Orthopedic Surgery, Hamamatsu University School of Medicine, 1-20-1, Handayama, Higashi-ku, Hamamatsu, Shizuoka 431-3192, Japan.
authors.forename: M
authors.initials: M
authors.lastname: Hanada
authors.affiliation: Department of Cell Biology and Anatomy, Hamamatsu University School of Medicine, 1-20-1, Handayama, Higashi-ku, Hamamatsu, Shizuoka 431-3192, Japan.
authors.forename: T
authors.initials: T
authors.lastname: Hayasaka
authors.affiliation: Department of Cell Biology and Anatomy, Hamamatsu University School of Medicine, 1-20-1, Handayama, Higashi-ku, Hamamatsu, Shizuoka 431-3192, Japan.
authors.forename: N
authors.initials: N
authors.lastname: Masaki
authors.affiliation: Department of Orthopedic Surgery, Hamamatsu University School of Medicine, 1-20-1, Handayama, Higashi-ku, Hamamatsu, Shizuoka 431-3192, Japan.
authors.forename: T
authors.initials: T
authors.lastname: Omura
authors.affiliation: Department of Orthopedic Surgery, Hamamatsu University School of Medicine, 1-20-1, Handayama, Higashi-ku, Hamamatsu, Shizuoka 431-3192, Japan.
authors.forename: D
authors.initials: D
authors.lastname: Xu
authors.affiliation: Department of Orthopedic Surgery, Hamamatsu University School of Medicine, 1-20-1, Handayama, Higashi-ku, Hamamatsu, Shizuoka 431-3192, Japan.
authors.forename: T
authors.initials: T
authors.lastname: Hasegawa
authors.affiliation: Department of Orthopedic Surgery, Hamamatsu University School of Medicine, 1-20-1, Handayama, Higashi-ku, Hamamatsu, Shizuoka 431-3192, Japan.
authors.forename: D
authors.initials: D
authors.lastname: Togawa
authors.affiliation: Department of Orthopedic Surgery, Hamamatsu University School of Medicine, 1-20-1, Handayama, Higashi-ku, Hamamatsu, Shizuoka 431-3192, Japan.
authors.forename: Y
authors.initials: Y
authors.lastname: Yamato
authors.affiliation: Department of Orthopedic Surgery, Hamamatsu University School of Medicine, 1-20-1, Handayama, Higashi-ku, Hamamatsu, Shizuoka 431-3192, Japan.
authors.forename: S
authors.initials: S
authors.lastname: Kobayashi
authors.affiliation: Department of Orthopedic Surgery, Hamamatsu University School of Medicine, 1-20-1, Handayama, Higashi-ku, Hamamatsu, Shizuoka 431-3192, Japan.
authors.forename: T
authors.initials: T
authors.lastname: Yasuda
authors.affiliation: Department of Orthopedic Surgery, Hamamatsu University School of Medicine, 1-20-1, Handayama, Higashi-ku, Hamamatsu, Shizuoka 431-3192, Japan.
authors.forename: Y
authors.initials: Y
authors.lastname: Matsuyama
authors.affiliation: Department of Cell Biology and Anatomy, Hamamatsu University School of Medicine, 1-20-1, Handayama, Higashi-ku, Hamamatsu, Shizuoka 431-3192, Japan. Electronic address: setou@hama-med.ac.jp.
authors.forename: M
authors.initials: M
authors.lastname: Setou
mesh_terms: D000818:Animals; D000911:Antibodies, Monoclonal / Q000494:pharmacology*; D004195:Disease Models, Animal; D004281:Docosahexaenoic Acids / Q000378:metabolism*; D005260:Female; D005904:Glial Fibrillary Acidic Protein; D006614:Hindlimb / Q000187:drug effects / Q000503:physiopathology; D015850:Interleukin-6 / Q000378:metabolism*; D008124:Locomotion / Q000187:drug effects / Q000502:physiology; D008264:Macrophages / Q000187:drug effects / Q000502:physiology; D008810:Mice, Inbred C57BL; D017628:Microglia / Q000187:drug effects / Q000502:physiology; D009419:Nerve Tissue Proteins / Q000378:metabolism; D018696:Neuroprotective Agents / Q000494:pharmacology*; D010713:Phosphatidylcholines / Q000378:metabolism*; D011897:Random Allocation; D020127:Recovery of Function / Q000187:drug effects / Q000502:physiology; D015398:Signal Transduction / Q000187:drug effects; D013116:Spinal Cord / Q000187:drug effects / Q000473:pathology / Q000503:physiopathology; D013119:Spinal Cord Injuries / Q000188:drug therapy* / Q000473:pathology / Q000503:physiopathology*; D013904:Thoracic Vertebrae
chemical_list: D000911:Antibodies, Monoclonal; D005904:Glial Fibrillary Acidic Protein; D015850:Interleukin-6; D009419:Nerve Tissue Proteins; D018696:Neuroprotective Agents; D010713:Phosphatidylcholines; C528900:glial fibrillary astrocytic protein, mouse; C577686:interleukin-6, mouse; D004281:Docosahexaenoic Acids
keywords: IL-6; docosahexaenoic acid; imaging mass spectrometry; phosphatidylcholine; phospholipids; spinal cord injury