1. TLR4 and TLR2 activation is differentially associated with age during Parkinson's disease.
- Author
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Rocha Sobrinho HMD, Silva DJD, Gomides LF, Dorta ML, Oliveira MAP, and Ribeiro-Dias F
- Subjects
- Adult, Aged, Cells, Cultured, Humans, Interleukin-10 metabolism, Lipopolysaccharides immunology, Lipoproteins immunology, Middle Aged, Risk, Toll-Like Receptor 2 agonists, Toll-Like Receptor 4 agonists, Tumor Necrosis Factor-alpha metabolism, Age Factors, Aging immunology, Parkinson Disease immunology, Toll-Like Receptor 2 metabolism, Toll-Like Receptor 4 metabolism
- Abstract
Parkinson's disease (PD) is an age-related neurodegenerative disease characterized by loss of dopaminergic neurons associated with neuroinflammation. Toll-like receptors (TLRs) are expressed in peripheral blood leukocytes and also in neurons and glial cells mediating inflammation. This study aimed to investigate the peripheral blood leukocyte response to TLR2 and TLR4 agonists in young and elderly PD patients. Two groups of patients with PD were evaluated (≤ 55 years old and ≥ 65 years old), age-matched with healthy controls (n = 26). Severity of PD was evaluated by Unified Parkinson's Disease Rating Scale (UPDRS). Whole blood cultures were stimulated with lipopolysaccharide (LPS), a TLR4 agonist or Pam
3 Cys (Pam), a TLR2 agonist. Tumor necrosis factor alpha (TNFα) and interleukin 10 (IL-10) were measured by immunoenzimatic assay. 6 h-TNFα production was increased after TLR4 stimulation, mainly in young PD patients, whereas TLR2-induced TNFα and IL-10 levels were decreased in PD patients independent of age (p < 0.05). A reverse correlation between LPS-induced TNFα production and age was observed in PD patients and controls, but TNFα induced by TLR2 agonist was not associated with age of PD patients or controls. TNFα production induced by TLR4 but not by TLR2 was reversely associated with the age at PD onset and disease duration. No associations between UPDRS scores and cytokine levels were detected. In conclusion, TLR4 and TLR2 responses seem to be differentially affected during PD. Data suggest that TLR2 deficiency in periphery is independent of age of the patients, age at PD onset, or PD duration.- Published
- 2018
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