TY - JOUR
T1 - Decreased toll-like receptor 2 and toll-like receptor 7/8-induced cytokines in Parkinson's disease patients
AU - Da Silva, Delson José
AU - Borges, Arissa Felipe
AU - Souza, Priscila Oliveira
AU - De Souza, Patrícia Reis
AU - De Barros Cardoso, Cristina Ribeiro
AU - Dorta, Miriam Leandro
AU - De Oliveira, Milton Adriano Pelli
AU - Teixeira, Antônio Lúcio
AU - Ribeiro-Dias, Fátima
N1 - Publisher Copyright:
© 2016 S. Karger AG, Basel.
PY - 2016/3/1
Y1 - 2016/3/1
N2 - Objectives: Toll-like receptors (TLRs) are expressed in several immune cells including blood monocytes and resident macrophages, such as microglia in the central nervous system. TLRs recognize pathogen- or damage-associated molecular patterns, leading to the release of inflammatory and toxic molecules, which can contribute to neuroinflammation associated with Parkinson's disease (PD). The aim of this study was to compare the potential of peripheral blood cells from PD patients or healthy subjects to produce cytokines after exposure to TLR agonists, and to investigate TLR2 and TLR4 expression on monocyte subsets. Methods: Twenty-one patients and 21 healthy controls were recruited. Patients were evaluated according to the Unified Parkinson's Disease Rating Scale, and Hoehn and Yahr stage. Cytokines were measured in supernatants of whole blood cultures after incubation with TLR2, TLR4, or TLR7/8 agonists, by cytometric bead array. Expression of CD14, CD16, TLR2, and TLR4 was analyzed by cytometry. Results: Patient blood cells produced lower levels of cytokines in response to TLR2 and also after TLR7/8/R848 activation than controls. Percentages of CD14+CD16+ or CD14+CD16- monocytes and TLR2 and TLR4 expression were similar between patients and controls. Conclusions: Blood leukocyte TLR2 and TLR7/8 responses are impaired in PD. This was neither associated with imbalance in monocyte subsets nor with TLR2/TLR4 expression on these cells. The association between a decreased TLR response in periphery and damage of brain in PD must be further investigated.
AB - Objectives: Toll-like receptors (TLRs) are expressed in several immune cells including blood monocytes and resident macrophages, such as microglia in the central nervous system. TLRs recognize pathogen- or damage-associated molecular patterns, leading to the release of inflammatory and toxic molecules, which can contribute to neuroinflammation associated with Parkinson's disease (PD). The aim of this study was to compare the potential of peripheral blood cells from PD patients or healthy subjects to produce cytokines after exposure to TLR agonists, and to investigate TLR2 and TLR4 expression on monocyte subsets. Methods: Twenty-one patients and 21 healthy controls were recruited. Patients were evaluated according to the Unified Parkinson's Disease Rating Scale, and Hoehn and Yahr stage. Cytokines were measured in supernatants of whole blood cultures after incubation with TLR2, TLR4, or TLR7/8 agonists, by cytometric bead array. Expression of CD14, CD16, TLR2, and TLR4 was analyzed by cytometry. Results: Patient blood cells produced lower levels of cytokines in response to TLR2 and also after TLR7/8/R848 activation than controls. Percentages of CD14+CD16+ or CD14+CD16- monocytes and TLR2 and TLR4 expression were similar between patients and controls. Conclusions: Blood leukocyte TLR2 and TLR7/8 responses are impaired in PD. This was neither associated with imbalance in monocyte subsets nor with TLR2/TLR4 expression on these cells. The association between a decreased TLR response in periphery and damage of brain in PD must be further investigated.
KW - Cytokines
KW - Monocytes
KW - Parkinson's disease
KW - Toll-like receptor 2
KW - Toll-like receptor 7/8
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U2 - 10.1159/000443238
DO - 10.1159/000443238
M3 - Article
C2 - 26886382
AN - SCOPUS:84958793731
SN - 1021-7401
VL - 23
SP - 58
EP - 66
JO - NeuroImmunoModulation
JF - NeuroImmunoModulation
IS - 1
ER -