Interleukin 15 expression in the CNS: Blockade of its activity prevents glial activation after an inflammatory injury

Functional and Systems Neurobiology Department, Cajal Institute, CSIC, Madrid, Spain.
Glia (Impact Factor: 6.03). 04/2008; 56(5):494-505. DOI: 10.1002/glia.20628
Source: PubMed


Although reactive glia formation after neuronal degeneration or traumatic damage is one of the hallmarks of central nervous system (CNS) injury, we have little information on the signals that direct activation of resting glia. IL-15, a pro-inflammatory cytokine involved in regulating the response of T and B cells, may be also key for the regulation of early inflammatory events in the nervous system. IL-15 was expressed in the CNS, most abundantly in cerebellum and hippocampus, mainly in astrocytes and in some projection neurons. Using a rodent model of acute inflammatory injury [lipopolysaccharide (LPS) injection], we found enhanced expression of IL-15 in both reactive astroglia and microglia, soon after CNS injury. Blockade of IL-15 activity with an antibody to the cytokine, reversed activation of both glial types, suggesting that IL-15 has a major role in the generation of gliotic tissue and in the regulation of neuroimmune responses. Because IL-15 appears to modulate the inflammatory environment acutely generated after CNS injury, regulating IL-15 expression seems a clear antiinflammatory therapy to improve the outcome of neurodegenerative diseases and CNS trauma.

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    • "The analysis of neurosphere differentiation was performed on cells growing under differentiation conditions (complete medium supplemented with 2% FBS; 4, 7, or 10 d) over glass coverslips coated with poly-llysine . Immunofluorescence staining was performed as previously described (Gomez-Nicola et al., 2008a). The cells were incubated with goat anti-mouse IL-15 (Santa Cruz Biotechnologies), guinea pig anti–mouse DCX (Chemicon), mouse anti–mouse nestin (Abcam), mouse anti–mouse GFAP (Chemicon), rabbit anti–mouse MBP (Abcam), mouse anti–mouse βIII tubulin (Sigma-Aldrich), or mouse anti–mouse O4 (Chemicon, Temecula, CA). "
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    • "Processing of U373MG cell samples and analysis of protein expression were performed as previously described (Gomez-Nicola et al., 2008a). Samples (20 μg protein/lane) were electrophoresed and transferred to nitrocellulose membranes (Whatman GmbH, Dassel, Germany). "
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    • "Additionally, western blotting analysis was used to test the CCR7 antibody specificity. The expression of CCR7 was quantified with the help of an image analysis system (AIS, Imaging Research Inc., Linton, England), using a 4× lens, as previously described (Gomez-Nicola et al., 2008a). "
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