Abstract
Impaired clearance of amyloid-β protein (Aβ) in the peripheral system is a crucial event in the pathogenesis of sporadic Alzheimer's disease (AD). Dysfunctional monocytes with deficient clearance of Aβ and increased secretion of pro-inflammatory factors in the periphery are considered to contribute to AD development. Multiple studies suggest that IL-4 can inhibit the inflammatory response and enhance the expression and activity of cathepsin protease associated with intracellular clearance of Aβ by monocytes. To investigate the effects of interleukin-4 (IL-4) on Aβ clearance and inflammatory response of monocytes in vitro. In this study, flow cytometry, confocal microscopy and ELISA techniques were used for measurement of Aβ clearance and its related mechanisms of monocytes. We found that the mean intracellular content and uptake ratios of Aβ42 in total monocytes, as well as in the CD14 + CD16- subset, were enhanced by IL-4, concomitant with the degradation of Aβ42 by monocytes. And IL-4 treatment also increased expression of scavenger receptor CD36 and Macrophage scavenger receptor 1 (MSR1) on monocytes. It was shown that IL-4 increased the Aβ immunoreactive area within lysosomal markers, including early endosome antigen 1 (EEA1), lysosome-associated membrane glycoprotein 1 and 2 (LAMP1 and 2) and Aβ degradative enzymes cathepsin B and S in monocytes, but reduced secretion of tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6) and interferon-γ (IFN-γ) by monocytes. Our study supports the role of IL-4 in regulating Aβ clearance and inflammatory response by monocytes, suggesting that IL-4 may have therapeutic potential for AD.
Published Version
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