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IL-17A is increased in the serum and in spinal cord CD8 and mast cells of ALS patients
The contribution of inflammation to neurodegenerative diseases is increasingly recognized, but the role of inflammation in sporadic amyotrophic lateral sclerosis (sALS) is not well understood and no animal model is available. We used enzyme-linked immunosorbent assays (ELISAs) to measure the cytokin...
Autores principales: | , , , , , , , , , , , , , , , , , , , |
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Formato: | Texto |
Lenguaje: | English |
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BioMed Central
2010
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2992053/ https://www.ncbi.nlm.nih.gov/pubmed/21062492 http://dx.doi.org/10.1186/1742-2094-7-76 |
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author | Fiala, Milan Chattopadhay, Madhuri La Cava, Antonio Tse, Eric Liu, Guanghao Lourenco, Elaine Eskin, Ascia Liu, Philip T Magpantay, Larry Tse, Stephen Mahanian, Michelle Weitzman, Rachel Tong, Jason Nguyen, Caroline Cho, Tiffany Koo, Patrick Sayre, James Martinez-Maza, Otoniel Rosenthal, Mark J Wiedau-Pazos, Martina |
author_facet | Fiala, Milan Chattopadhay, Madhuri La Cava, Antonio Tse, Eric Liu, Guanghao Lourenco, Elaine Eskin, Ascia Liu, Philip T Magpantay, Larry Tse, Stephen Mahanian, Michelle Weitzman, Rachel Tong, Jason Nguyen, Caroline Cho, Tiffany Koo, Patrick Sayre, James Martinez-Maza, Otoniel Rosenthal, Mark J Wiedau-Pazos, Martina |
author_sort | Fiala, Milan |
collection | PubMed |
description | The contribution of inflammation to neurodegenerative diseases is increasingly recognized, but the role of inflammation in sporadic amyotrophic lateral sclerosis (sALS) is not well understood and no animal model is available. We used enzyme-linked immunosorbent assays (ELISAs) to measure the cytokine interleukin-17A (IL-17A) in the serum of ALS patients (n = 32; 28 sporadic ALS (sALS) and 4 familial ALS (fALS)) and control subjects (n = 14; 10 healthy subjects and 4 with autoimmune disorders). IL-17A serum concentrations were 5767 ± 2700 pg/ml (mean ± SEM) in sALS patients and 937 ± 927 pg/ml in fALS patients in comparison to 7 ± 2 pg/ml in control subjects without autoimmune disorders (p = 0.008 ALS patients vs. control subjects by Mann-Whitney test). Sixty-four percent of patients and no control subjects had IL-17A serum concentrations > 50 pg/ml (p = 0.003 ALS patients vs. healthy subjects by Fisher's exact test). The spinal cords of sALS (n = 8), but not control subjects (n = 4), were infiltrated by interleukin-1β- (IL-1β-), and tumor necrosis factor-α-positive macrophages (co-localizing with neurons), IL-17A-positive CD8 cells, and IL-17A-positive mast cells. Mononuclear cells treated with aggregated forms of wild type superoxide dismutase-1 (SOD-1) showed induction of the cytokines IL-1β, interleukin-6 (IL-6), and interleukin-23 (IL-23) that may be responsible for induction of IL-17A. In a microarray analysis of 28,869 genes, stimulation of peripheral blood mononuclear cells by mutant superoxide dismutase-1 induced four-fold higher transcripts of interleukin-1α (IL-1α), IL-6, CCL20, matrix metallopeptidase 1, and tissue factor pathway inhibitor 2 in mononuclear cells of patients as compared to controls, whereas the anti-inflammatory cytokine interleukin-10 (IL-10) was increased in mononuclear cells of control subjects. Aggregated wild type SOD-1 in sALS neurons could induce in mononuclear cells the cytokines inducing chronic inflammation in sALS spinal cord, in particular IL-6 and IL-17A, damaging neurons. Immune modulation of chronic inflammation may be a new approach to sALS. |
format | Text |
id | pubmed-2992053 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2010 |
publisher | BioMed Central |
record_format | MEDLINE/PubMed |
spelling | pubmed-29920532010-11-26 IL-17A is increased in the serum and in spinal cord CD8 and mast cells of ALS patients Fiala, Milan Chattopadhay, Madhuri La Cava, Antonio Tse, Eric Liu, Guanghao Lourenco, Elaine Eskin, Ascia Liu, Philip T Magpantay, Larry Tse, Stephen Mahanian, Michelle Weitzman, Rachel Tong, Jason Nguyen, Caroline Cho, Tiffany Koo, Patrick Sayre, James Martinez-Maza, Otoniel Rosenthal, Mark J Wiedau-Pazos, Martina J Neuroinflammation Case Study The contribution of inflammation to neurodegenerative diseases is increasingly recognized, but the role of inflammation in sporadic amyotrophic lateral sclerosis (sALS) is not well understood and no animal model is available. We used enzyme-linked immunosorbent assays (ELISAs) to measure the cytokine interleukin-17A (IL-17A) in the serum of ALS patients (n = 32; 28 sporadic ALS (sALS) and 4 familial ALS (fALS)) and control subjects (n = 14; 10 healthy subjects and 4 with autoimmune disorders). IL-17A serum concentrations were 5767 ± 2700 pg/ml (mean ± SEM) in sALS patients and 937 ± 927 pg/ml in fALS patients in comparison to 7 ± 2 pg/ml in control subjects without autoimmune disorders (p = 0.008 ALS patients vs. control subjects by Mann-Whitney test). Sixty-four percent of patients and no control subjects had IL-17A serum concentrations > 50 pg/ml (p = 0.003 ALS patients vs. healthy subjects by Fisher's exact test). The spinal cords of sALS (n = 8), but not control subjects (n = 4), were infiltrated by interleukin-1β- (IL-1β-), and tumor necrosis factor-α-positive macrophages (co-localizing with neurons), IL-17A-positive CD8 cells, and IL-17A-positive mast cells. Mononuclear cells treated with aggregated forms of wild type superoxide dismutase-1 (SOD-1) showed induction of the cytokines IL-1β, interleukin-6 (IL-6), and interleukin-23 (IL-23) that may be responsible for induction of IL-17A. In a microarray analysis of 28,869 genes, stimulation of peripheral blood mononuclear cells by mutant superoxide dismutase-1 induced four-fold higher transcripts of interleukin-1α (IL-1α), IL-6, CCL20, matrix metallopeptidase 1, and tissue factor pathway inhibitor 2 in mononuclear cells of patients as compared to controls, whereas the anti-inflammatory cytokine interleukin-10 (IL-10) was increased in mononuclear cells of control subjects. Aggregated wild type SOD-1 in sALS neurons could induce in mononuclear cells the cytokines inducing chronic inflammation in sALS spinal cord, in particular IL-6 and IL-17A, damaging neurons. Immune modulation of chronic inflammation may be a new approach to sALS. BioMed Central 2010-11-09 /pmc/articles/PMC2992053/ /pubmed/21062492 http://dx.doi.org/10.1186/1742-2094-7-76 Text en Copyright ©2010 Fiala et al; licensee BioMed Central Ltd. http://creativecommons.org/licenses/by/2.0 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. |
spellingShingle | Case Study Fiala, Milan Chattopadhay, Madhuri La Cava, Antonio Tse, Eric Liu, Guanghao Lourenco, Elaine Eskin, Ascia Liu, Philip T Magpantay, Larry Tse, Stephen Mahanian, Michelle Weitzman, Rachel Tong, Jason Nguyen, Caroline Cho, Tiffany Koo, Patrick Sayre, James Martinez-Maza, Otoniel Rosenthal, Mark J Wiedau-Pazos, Martina IL-17A is increased in the serum and in spinal cord CD8 and mast cells of ALS patients |
title | IL-17A is increased in the serum and in spinal cord CD8 and mast cells of ALS patients |
title_full | IL-17A is increased in the serum and in spinal cord CD8 and mast cells of ALS patients |
title_fullStr | IL-17A is increased in the serum and in spinal cord CD8 and mast cells of ALS patients |
title_full_unstemmed | IL-17A is increased in the serum and in spinal cord CD8 and mast cells of ALS patients |
title_short | IL-17A is increased in the serum and in spinal cord CD8 and mast cells of ALS patients |
title_sort | il-17a is increased in the serum and in spinal cord cd8 and mast cells of als patients |
topic | Case Study |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2992053/ https://www.ncbi.nlm.nih.gov/pubmed/21062492 http://dx.doi.org/10.1186/1742-2094-7-76 |
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