Neuroinflamação na doença de Parkinson: avaliação de citocinas induzidas via Toll like receptors em células do sangue periférico
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Data
2014-08-29
Autores
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Editor
Universidade Federal de Goiás
Resumo
Parkinson’s disease (PD) is as a neurodegenerative disorder caused by
neuron loss in the substantia nigra, which produces dopamine. Evidences
suggest that several inflammatory cytokines are enhanced in the brain and
blood of patients presenting with PD. These cytokines might be induced by
Toll-like receptor (TLR) activation. In peripheral blood, monocytes express
TLR and may participate in the immunopathogenicity of neurodegenerative
diseases. The objectives of this work were: carry out a literature review
about neuroinflammation in PD; assess possible alterations in production
of inflammatory cytokines in blood cultures of patients presenting with
PD activated by TLR agonists; evaluate the percentages of the two main
monocyte subpopulations, as well as TLR2 and TLR4 expression in these
subpopulations in peripheral blood of patients presenting with PD. Patients
presenting with PD (n = 31) and healthy individuals (n = 31), matched by
gender and age, were evaluated and the patients were assessed regarding
the severity of their neurological and psychiatric symptoms using the Hoen &
Yahr scale (H&Y) and the Unified Parkinson’s Disease Rating Scale (UPDRS).
Blood cultures were activated with TLR2 agonists (Pam3Cys), TLR4 (LPS),
or TLR7/8 (R848). Cytokines (TNF, IL-1β, IL-6, IL-12p70, and IL-10) were
Abstract 12
quantified in the serum and supernatant of blood cultures using Cytometer
bead array. Monocytes (CD14+CD16– and CD14+CD16+) and TLR2 and TLR4
expression were identified using flow cytometry. Cytokine concentrations in
the serum of patients and controls were similar and no significant association
was found between cytokine concentrations and UPDRS scores. However,
after activation of blood cultures of patients, a significant decreased response
to TLR2 (TNF, IL-1β, IL-6, IL-10) and TLR7/8 (IL-6) agonists was observed.
No correlation was observed between the concentrations of cytokines
induced by TLR2 or TLR7/8 agonists and UPDRS scores. The percentages of
monocytes CD14+CD16– and CD14+CD16+ did not significantly differ between
patients and controls, and no alterations in TLR2 or TLR4 expressions were
detected in these monocyte subpopulations in patients. The results indicate
that leukocytes, especially monocytes, of patients presenting with PD show
decreased capacity to respond to the activation via TLR2. This decrease
may be associated with the previous activation of TLR2 in vivo, making the
cells tolerant to new stimuli ex vivo. Assessing the activation of monocytes in
peripheral blood, via TLR, may help the evaluation of the neurodegenerative/
neuroinflammatory process in PD, contributing to a better understanding of
the pathophysiology of this disease.
Descrição
Palavras-chave
Doença de Parkinson , TLR2 , TLR7/8 , Monócitos , Citocinas , Parkinson’s disease , TLR2 , TLR7/8 , Monocytes , Cytokines
Citação
SILVA, D. J. da. Neuroinflamação na doença de Parkinson: avaliação de citocinas induzidas via Toll like receptors em células do sangue periférico. 2014. 106 f. Tese (Doutorado em Saúde Coletiva) - Universidade Federal de Goiás, Goiânia, 2014.