title: Effects of astrocyte-targeted production of interleukin-6 in the mouse on the host response to nerve injury.
abstract: Interleukin-6 (IL-6) is a pleiotropic cytokine with a key role in the control of inflammatory/immune responses. In the central nervous system (CNS), an increase in IL-6 occurs in a wide range of pathological conditions such as excitotoxicity and traumatic brain injury. We evaluated the effects of astrocyte-targeted production of IL-6 in the CNS in the sterile-nerve injury model of facial nerve axotomy. To accomplish this, facial nerve transection was performed in transgenic mice (glial fibrillary acidic protein [GFAP]-IL6Tg) with IL-6 production under the GFAP promoter. Neuronal death, glial activation, lymphocyte recruitment, and integrin expression were evaluated by immunohistochemistry and flow cytometry from 3 to 28 days postinjury. Our findings revealed an increase in motor neuron cell death in GFAP-IL6Tg mice correlating with changes in the microglial activation pattern, characterized principally by less attachment to neurons and reduced expression of both CD11b and CD18. We also found a higher CD4(+) T-lymphocyte recruitment in GFAP-IL6Tg mice. In addition, changes in the expression pattern of different integrins and their receptors were observed in transgenic animals. Specifically, alterations in osteopontin expression in motor neurons and its receptors CD44 and CD49e in lymphocytes and microglia, respectively, which may account for the variations related to glial reactivity and lymphocyte infiltration. In conclusion, our results indicated that forced local production of IL-6 has a direct impact on the outcome of nerve injury in the CNS inducing an increase in neurodegeneration, changes in glial response, and lymphocyte recruitment as well as in the expression of different integrins and their receptors.
authors.affiliation: Department of Cell Biology, Physiology and Immunology, Institute of Neuroscience, Autonomous University of Barcelona, Bellaterra, 08193, Spain.
authors.forename: Beatriz
authors.initials: B
authors.lastname: Almolda
authors.forename: Nàdia
authors.initials: N
authors.lastname: Villacampa
authors.forename: Peter
authors.initials: P
authors.lastname: Manders
authors.forename: Juan
authors.initials: J
authors.lastname: Hidalgo
authors.forename: Iain L
authors.initials: IL
authors.lastname: Campbell
authors.forename: Berta
authors.initials: B
authors.lastname: González
authors.forename: Bernardo
authors.initials: B
authors.lastname: Castellano
mesh_terms: D000818:Animals; D001253:Astrocytes / Q000502:physiology*; D039481:CD11b Antigen / Q000378:metabolism; D018821:CD18 Antigens / Q000378:metabolism; D015496:CD4-Positive T-Lymphocytes / Q000502:physiology; D016923:Cell Death / Q000502:physiology; D004195:Disease Models, Animal; D020220:Facial Nerve Injuries / Q000503:physiopathology*; D005904:Glial Fibrillary Acidic Protein; D018960:Hyaluronan Receptors / Q000378:metabolism; D039482:Integrin alpha5 / Q000378:metabolism; D016023:Integrins / Q000378:metabolism; D015850:Interleukin-6 / Q000235:genetics / Q000378:metabolism*; D008214:Lymphocytes / Q000378:metabolism; D008822:Mice, Transgenic; D017628:Microglia / Q000502:physiology; D009046:Motor Neurons / Q000502:physiology; D009410:Nerve Degeneration / Q000503:physiopathology; D009419:Nerve Tissue Proteins / Q000235:genetics / Q000378:metabolism; D009457:Neuroglia / Q000502:physiology; D009474:Neurons / Q000502:physiology; D053495:Osteopontin / Q000378:metabolism
chemical_list: D039481:CD11b Antigen; D018821:CD18 Antigens; C476399:Cd44 protein, mouse; D005904:Glial Fibrillary Acidic Protein; D018960:Hyaluronan Receptors; D039482:Integrin alpha5; D016023:Integrins; D015850:Interleukin-6; D009419:Nerve Tissue Proteins; C506896:Spp1 protein, mouse; C528900:glial fibrillary astrocytic protein, mouse; C577686:interleukin-6, mouse; D053495:Osteopontin
keywords: CD44; facial nerve axotomy; lymphocytes; microglia; osteopontin; transgenic animal