All-trans-retinoic acid modulates nitric oxide and interleukin-17A production by peripheral blood mononuclear cells from patients with Alzheimer's disease.
BACKGROUND
Alzheimer's disease (AD), the most common form of dementia in the elderly, is a neurodegenerative disorder associated with a complex pathophysiology. It is accepted that inflammation contributes to the pathogenesis of AD. All-trans-retinoic acid (ATRA) is a bioactive derivative of vitamin A that has shown immunomodulatory effects in many immune disorders.


OBJECTIVE
In our study, we aimed to investigate in vitro immunomodulatory effects of ATRA on inducible nitric oxide synthase (iNOS) expression and interleukin-17A production during AD.


METHODS
Peripheral blood mononuclear cells (PBMCs) isolated from 30 Algerian AD patients and 14 age-matched nondemented controls were treated (or not) with ATRA. Production of NO and IL-17A in culture media was measured by the modified Griess method and enzyme-linked immunosorbent assay, respectively. Expression of iNOS in PBMCs was examined by fluorescence immunostaining.


RESULTS
Our results showed higher spontaneous in vitro production of NO related to overexpression of iNOS in AD patients compared to controls. Remarkably, ATRA treatment showed an important downregulatory effect on NO production and iNOS expression in patients. This effect was associated with a reduction in IL-17A production and increased IL-10 release.


CONCLUSIONS
Taken together, our results indicate that ATRA exerts anti-inflammatory effects in AD. Furthermore, ATRA represents a promising tool for monitoring inflammatory responses associated with disease progression.
Cytokines and NO Synthases, Immunity and Pathogeny Team, Laboratory of Cellular and Molecular Biology (LBCM), Faculty of Biological Sciences, University of Sciences and Technology Houari Boumediene (USTHB), Algiers, Algeria.
Nassima
N
Behairi
Mourad
M
Belkhelfa
Hamida
H
Mesbah-Amroun
Hayet
H
Rafa
Soreya
S
Belarbi
Meriem
M
Tazir
Chafia
C
Touil-Boukoffa
D000368:Aged; D000369:Aged, 80 and over; D000544:Alzheimer Disease / Q000473:pathology*; D000704:Analysis of Variance; D000970:Antineoplastic Agents / Q000494:pharmacology*; D016022:Case-Control Studies; D002478:Cells, Cultured; D005260:Female; D006801:Humans; D020381:Interleukin-17 / Q000097:blood*; D007963:Leukocytes, Mononuclear / Q000187:drug effects*; D008297:Male; D008875:Middle Aged; D009569:Nitric Oxide / Q000097:blood*; D014212:Tretinoin / Q000494:pharmacology*
D000970:Antineoplastic Agents; D020381:Interleukin-17; D009569:Nitric Oxide; D014212:Tretinoin