Anti-inflammatory effects of 9-cis-retinoic acid on β-amyloid treated human microglial cells

Objective: Alzheimer's disease (AD) is a neurodegenerative disease that abolishes cognitive and analytical abilities to perform basic day-to-day tasks. Microglia are involved in AD-associated neuroinflammation in response to amyloid beta-peptide (A beta). This study focused on observing the immunomodulatory effects of 9-cis-retinoic acid (9-Cis-RA) the active metabolite of vitamin A, on A beta-treated human microglial HMO6 cells. Methods: HMO6 cells were treated with A beta 42 in the absence or presence of 9-cis-RA, and the expression of M1-and M2-associated molecules, Toll like receptors (TLRs), and triggering receptor expressed on myeloid cells 2 (TREM2) were examined. Results: The levels of M1-markers [cluster of differentiation (CD86) and inducible nitric oxide synthase (iNOS)] and -cytokines [tumor necrosis factor (TNF-alpha), interleukin (IL)-6, and IL-1 beta], inflammatory receptors (TLR2 and TLR4), and reactive oxygen species increased significantly in A beta-treated HMO6 cells. In contrast, the levels of M2-markers (CD206 and arginase-1) and -cytokines (IL-10, IL-4, and C-C motif chemokine ligand 17) the anti-inflammatory receptor TLR10 was significantly suppressed. However, 9-cis-RA treatment reversed the A beta-induced upregulation of expression of M1-associated molecules and upregulated the expression of M2-associated molecules. Moreover, 9-cis-RA treatment augmented A beta uptake by HMO6 cells, possibly by increasing the cell surface protein levels of TREM2, which is a receptor of A beta that promotes A beta phagocytosis by microglia. Conclusion: Our results suggest that 9-cis-RA is a potential therapeutic agent for AD.