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Blockade of IL-15 activity inhibits microglial activation through the NFkappaB, p38, and ERK1/2 pathways, reducing cytokine and chemokine release

Gomez-Nicola, Diego, Valle-Argos, Beatriz and Nieto-Sampedro, Manuel (2010) Blockade of IL-15 activity inhibits microglial activation through the NFkappaB, p38, and ERK1/2 pathways, reducing cytokine and chemokine release Glia, 58, (3), pp. 264-276. (doi:10.1002/glia.20920). (PMID:19610094).

Record type: Article

Abstract

Reactive glia formation is one of the hallmarks of damage to the CNS, but little information exists on the signals that direct its activation. Microglial cells are the main regulators of both innate and adaptative immune responses in the CNS. The proinflammatory cytokine IL-15 is involved in regulating the response of T and B cells, playing a key role in regulating nervous system inflammatory events. We have used a microglial culture model of inflammation induced by LPS and IFNgamma to evaluate the role of IL-15 in the proinflammatory response. Our results indicate that IL-15 is necessary for the reactive response, its deficiency (IL-15-/-) leading to the development of a defective proinflammatory response. Blockade of IL-15, both with blocking antibodies or with the ganglioside Neurostatin, inhibited the activation of the NFkappaB pathway, decreasing iNOS expression and NO production. Inhibiting IL-15 signaling also blocked the activation of the mitogen-activated protein kinase (MAPK) pathways ERK1/2 and p38. The major consequence of these inhibitory effects, analyzed using cytokine antibody arrays, was a severe decrease in the production of chemokines, cytokines and growth factors, like CCL17, CCL19, IL-12, or TIMP-1, that are essential for the development of the phenotypic changes of glial activation. In conclusion, activation of the IL-15 system seems a necessary step for the development of glial reactivity and the regulation of the physiology of glial cells. Modulating IL-15 activity opens the possibility of developing new strategies to control gliotic events upon inflammatory stimulation.

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More information

e-pub ahead of print date: 16 July 2009
Published date: February 2010
Keywords: inflammation, MAPKs, IL-15 knockout mice, gliosis, neurostatin, antibody arrays
Organisations: Biomedicine

Identifiers

Local EPrints ID: 333260
URI: http://eprints.soton.ac.uk/id/eprint/333260
ISSN: 0894-1491
PURE UUID: 44184601-fa99-422d-8df2-8d2fda5b63cb
ORCID for Diego Gomez-Nicola: ORCID iD orcid.org/0000-0002-5316-2682

Catalogue record

Date deposited: 02 Mar 2012 16:48
Last modified: 18 Jul 2017 06:13

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Contributors

Author: Beatriz Valle-Argos
Author: Manuel Nieto-Sampedro

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