title: Interleukin-10 overexpression does not synergize with the neuroprotective action of RGD-containing vectors after postnatal brain excitotoxicity but modulates the main inflammatory cell responses.
abstract: Antiinflammatory cytokines such as interleukin-10 (IL-10) have been used to modulate and terminate inflammation and provide neuroprotection. Recently, we reported that the modular recombinant transfection vector NLSCt is an efficient tool for transgene overexpression in vivo, which induces neuroprotection as a result of its RGD-mediated integrin-interacting capacity. We here sought to evaluate the putative synergic neuroprotective action exerted by IL-10 overexpression using NLSCt as a transfection vector after an excitotoxic injury to the postnatal rat brain. For this purpose, lesion volume, neurodegeneration, astroglial and microglial responses, neutrophil infiltration, and proinflammatory cytokine production were analyzed at several survival times after intracortical NMDA injection in postnatal day 9 rats, followed by injection of NLSCt combined with the IL-10 gene, a control transgene, or saline vehicle solution. Our results show no combined neuroprotective effect between RGD-interacting vectors and IL-10 gene therapy; instead, IL-10 overexpression using NLSCt as transfection vector increased lesion volume and neuronal degeneration at 12 hr and 3 days postlesion. In parallel, NLSCt/IL-10 treated animals displayed increased density of neutrophils and microglia/macrophages, and a reduced astroglial content of GFAP and vimentin. Moreover, NLSCt/IL-10 treated animals did not show any variation in interleukin-1β or tumor necrosis factor-α expression but a slight increase in interleukin-6 content at 7 days postlesion. In conclusion, overexpression of IL-10 by using NLSCt transfection vector did not synergistically neuroprotect the excitotoxically damaged postnatal rat brain but induced changes in the astroglial and microglial and inflammatory cell response.
authors.affiliation: Unit of Medical Histology, Department of Cell Biology, Physiology and Immunology and Neuroscience Institute, Autonomous University of Barcelona, Barcelona, Spain. paug@sescam.jccm.es
authors.forename: Pau
authors.initials: P
authors.lastname: Gonzalez
authors.forename: Hugo
authors.initials: H
authors.lastname: Peluffo
authors.forename: Laia
authors.initials: L
authors.lastname: Acarin
authors.forename: Antonio
authors.initials: A
authors.lastname: Villaverde
authors.forename: Berta
authors.initials: B
authors.lastname: Gonzalez
authors.forename: Bernardo
authors.initials: B
authors.lastname: Castellano
mesh_terms: D000704:Analysis of Variance; D000818:Animals; D000831:Animals, Newborn; D039481:CD11b Antigen / Q000378:metabolism; D016923:Cell Death / Q000187:drug effects; D016207:Cytokines / Q000378:metabolism*; D004195:Disease Models, Animal; D004797:Enzyme-Linked Immunosorbent Assay / Q000379:methods; D005260:Female; D005452:Fluoresceins; D005786:Gene Expression Regulation / Q000187:drug effects; D005822:Genetic Vectors / Q000627:therapeutic use; D005904:Glial Fibrillary Acidic Protein / Q000378:metabolism; D006639:Histidine / Q000031:analogs & derivatives / Q000378:metabolism; D016753:Interleukin-10 / Q000235:genetics / Q000378:metabolism*; D008264:Macrophages / Q000187:drug effects / Q000502:physiology; D008297:Male; D016202:N-Methylaspartate / Q000633:toxicity; D009457:Neuroglia / Q000187:drug effects / Q000502:physiology; D018696:Neuroprotective Agents / Q000378:metabolism / Q000627:therapeutic use*; D020258:Neurotoxicity Syndromes / Q000209:etiology / Q000473:pathology* / Q000628:therapy*; D009504:Neutrophils / Q000187:drug effects / Q000502:physiology; D009842:Oligopeptides / Q000378:metabolism / Q000627:therapeutic use*; D009930:Organic Chemicals; D009195:Peroxidase / Q000378:metabolism; D037121:Plant Lectins; D051381:Rats; D020318:Rats, Long-Evans; D014161:Transduction, Genetic / Q000379:methods; D014746:Vimentin / Q000378:metabolism
chemical_list: D039481:CD11b Antigen; D016207:Cytokines; D005452:Fluoresceins; D005904:Glial Fibrillary Acidic Protein; D018696:Neuroprotective Agents; D009842:Oligopeptides; D009930:Organic Chemicals; D037121:Plant Lectins; D014746:Vimentin; C435731:fluoro jade; C034981:tomato lectin; D016753:Interleukin-10; D006639:Histidine; D016202:N-Methylaspartate; C047981:arginyl-glycyl-aspartic acid; D009195:Peroxidase; C005436:phosphohistidine