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Role of IL-15 in spinal cord and sciatic nerve after chronic constriction injury: regulation of macrophage and T-cell infiltration

Role of IL-15 in spinal cord and sciatic nerve after chronic constriction injury: regulation of macrophage and T-cell infiltration
Role of IL-15 in spinal cord and sciatic nerve after chronic constriction injury: regulation of macrophage and T-cell infiltration
The release of inflammatory mediators from immune and glial cells either in the peripheral or CNS may have an important role in the development of physiopathological processes such as neuropathic pain. Microglial, then astrocytic activation in the spinal cord, lead to chronic inflammation, alteration of neuronal physiology and neuropathic pain. Standard experimental models of neuropathic pain include an important peripheral inflammatory component, which involves prominent immune cell activation and infiltration. Among potential immunomodulators, the T-cell cytokine interleukin-15 (IL-15) has a key role in regulating immune cell activation and glial reactivity after CNS injury. Here we show, using the model of chronic constriction of the sciatic nerve (CCI), that IL-15 is essential for the development of the early inflammatory events in the spinal cord after a peripheral lesion that generates neuropathic pain. IL-15 expression in the spinal cord was identified in both astroglial and microglial cells and was present during the initial gliotic and inflammatory (NFkappaB) response to injury. The expression of IL-15 was also identified as a cue for macrophage and T-cell activation and infiltration in the sciatic nerve, as shown by intraneural injection of the cytokine and activity blockage approaches. We conclude that the regulation of IL-15 and hence the initial events following its expression after peripheral nerve injury could have a future therapeutic potential in the reduction of neuroinflammation.
astrocytes, cytokines, inflammation, microglia, neuropathic pain, NF?B
0022-3042
1741-1752
Gomez-Nicola, D.
0680aa66-9dee-47cf-a8d3-e39c988f85b5
Valle-Argos, B.
4fddaa71-c0aa-4b95-b464-8bdb592428a2
Suardíaz, M.
2eb4e225-df7c-4a53-8d45-624c3bcf1f05
Taylor, J.S.
5d5056b1-ec26-46ed-a3a9-74a3fdaf2b3f
Nieto-Sampedro, M.
0d587598-0d8a-4d8e-9e12-e802068bdd53
Gomez-Nicola, D.
0680aa66-9dee-47cf-a8d3-e39c988f85b5
Valle-Argos, B.
4fddaa71-c0aa-4b95-b464-8bdb592428a2
Suardíaz, M.
2eb4e225-df7c-4a53-8d45-624c3bcf1f05
Taylor, J.S.
5d5056b1-ec26-46ed-a3a9-74a3fdaf2b3f
Nieto-Sampedro, M.
0d587598-0d8a-4d8e-9e12-e802068bdd53

Gomez-Nicola, D., Valle-Argos, B., Suardíaz, M., Taylor, J.S. and Nieto-Sampedro, M. (2008) Role of IL-15 in spinal cord and sciatic nerve after chronic constriction injury: regulation of macrophage and T-cell infiltration. Journal of Neurochemistry, 107 (6), 1741-1752. (doi:10.1111/j.1471-4159.2008.05746.x). (PMID:19014377)

Record type: Article

Abstract

The release of inflammatory mediators from immune and glial cells either in the peripheral or CNS may have an important role in the development of physiopathological processes such as neuropathic pain. Microglial, then astrocytic activation in the spinal cord, lead to chronic inflammation, alteration of neuronal physiology and neuropathic pain. Standard experimental models of neuropathic pain include an important peripheral inflammatory component, which involves prominent immune cell activation and infiltration. Among potential immunomodulators, the T-cell cytokine interleukin-15 (IL-15) has a key role in regulating immune cell activation and glial reactivity after CNS injury. Here we show, using the model of chronic constriction of the sciatic nerve (CCI), that IL-15 is essential for the development of the early inflammatory events in the spinal cord after a peripheral lesion that generates neuropathic pain. IL-15 expression in the spinal cord was identified in both astroglial and microglial cells and was present during the initial gliotic and inflammatory (NFkappaB) response to injury. The expression of IL-15 was also identified as a cue for macrophage and T-cell activation and infiltration in the sciatic nerve, as shown by intraneural injection of the cytokine and activity blockage approaches. We conclude that the regulation of IL-15 and hence the initial events following its expression after peripheral nerve injury could have a future therapeutic potential in the reduction of neuroinflammation.

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More information

e-pub ahead of print date: 20 October 2008
Published date: December 2008
Keywords: astrocytes, cytokines, inflammation, microglia, neuropathic pain, NF?B
Organisations: Biomedicine

Identifiers

Local EPrints ID: 333262
URI: http://eprints.soton.ac.uk/id/eprint/333262
ISSN: 0022-3042
PURE UUID: 36cbb048-bc55-41ef-94a3-ea55a2be1a9c
ORCID for D. Gomez-Nicola: ORCID iD orcid.org/0000-0002-5316-2682

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Date deposited: 02 Mar 2012 16:43
Last modified: 15 Mar 2024 03:37

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Contributors

Author: D. Gomez-Nicola ORCID iD
Author: B. Valle-Argos
Author: M. Suardíaz
Author: J.S. Taylor
Author: M. Nieto-Sampedro

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