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.

Pau Gonzalez (1, 2) , Hugo Peluffo (3) , Laia Acarin (1) , Antonio Villaverde (4, 5) , Berta Gonzalez (1) , Bernardo Castellano (1)

1 Unit of Medical Histology, Department of Cell Biology
2 Molecular Neurology Laboratory
3 Institut Pasteur de Montevideo
4 Institute of Biology and Biomedicine and Department of Genetics and Microbiology
5 CIBER-BBN - Networking Biomedical Research Center in Bioengineering, Biomaterials and Nanomedicine

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.

Domaines: Neurosciences [q-bio.NC]

Pau Gonzalez, Hugo Peluffo, Laia Acarin, Antonio Villaverde, Berta Gonzalez, et al.. 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.. Journal of Neuroscience Research, 2012, 90 (1), pp.143-59. ⟨10.1002/jnr.22741⟩. ⟨pasteur-00686279⟩