Production of IL-16 correlates with CD4+ Th1 inflammation and phosphorylation of axonal cytoskeleton in multiple scleros
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BioMed Central
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Production of IL-16 correlates with CD4+ Th1 inflammation and phosphorylation of axonal cytoskeleton in multiple sclerosis lesions Dusanka S Skundric*1,2, Juan Cai1, William W Cruikshank3 and Djordje Gveric4 Address: 1Department of Neurology, Wayne State University School of Medicine, Detroit, MI 48201, USA, 2Department of Immunology and Microbiology, Wayne State University School of Medicine, Detroit, MI 48201, USA, 3Pulmonary Center Boston University School of Medicine, Boston, MA 02118, USA and 4Department of Neuroinflammation, Institute of Neurology, University College London WC1N 1PJ, UK Email: Dusanka S Skundric* - [email protected]; Juan Cai - [email protected]; William W Cruikshank - [email protected]; Djordje Gveric - [email protected] * Corresponding author
Published: 26 May 2006 Journal of Neuroinflammation 2006, 3:13
doi:10.1186/1742-2094-3-13
Received: 07 April 2006 Accepted: 26 May 2006
This article is available from: http://www.jneuroinflammation.com/content/3/1/13 © 2006 Skundric et al; licensee BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
Abstract Background: Multiple sclerosis (MS) is a central nervous system-specific autoimmune, demyelinating and neurodegenerative disease. Infiltration of lesions by autoaggressive, myelin-specific CD4+Th1 cells correlates with clinical manifestations of disease. The cytokine IL-16 is a CD4+ T cell-specific chemoattractant that is biased towards CD4+ Th1 cells. IL-16 precursor is constitutively expressed in lymphocytes and during CD4+ T cell activation; active caspase-3 cleaves and releases C-terminal bioactive IL-16. Previously, we used an animal model of MS to demonstrate an important role for IL-16 in regulation of autoimmune inflammation and subsequent axonal damage. This role of IL-16 in MS is largely unexplored. Here we examine the regulation of IL-16 in relation to CD4+ Th1 infiltration and inflammation-related changes of axonal cytoskeleton in MS lesions. Methods: We measured relative levels of IL-16, active caspase-3, T-bet, Stat-1 (Tyr 701), and phosphorylated NF(M+H), in brain and spinal cord lesions from MS autopsies, using western blot analysis. We examined samples from 39 MS cases, which included acute, subacute and chronic lesions, as well as adjacent, normal-appearing white and grey matter. All samples were taken from patients with relapsing remitting clinical disease. We employed two-color immunostaining and confocal microscopy to identify phenotypes of IL-16-containing cells in frozen tissue sections from MS lesions. Results: We found markedly increased levels of pro- and secreted IL-16 (80 kD and 22 kD, respectively) in MS lesions compared to controls. Levels of IL-16 peaked in acute, diminished in subacute, and were elevated again
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