The amelioration of phagocytic ability in microglial cells by curcumin through the inhibition of EMF-induced pro-inflammatory responses

Abstract

BackgroundInsufficient clearance by microglial cells, prevalent in several neurological conditions and diseases, is intricately intertwined with MFG-E8 expression and inflammatory responses. Electromagnetic field (EMF) exposure can elicit the pro-inflammatory activation and may also trigger an alteration of the clearance function in microglial cells. Curcumin has important roles in the anti-inflammatory and phagocytic process. Here, we evaluated the ability of curcumin to ameliorate the phagocytic ability of EMF-exposed microglial cells (N9 cells) and documented relative pathways.MethodsN9 cells were pretreated with or without recombinant murine MFG-E8 (rmMFG-E8), curcumin and an antibody of toll-like receptor 4 (anti-TLR4), and subsequently treated with EMF or a sham exposure. Their phagocytic ability was evaluated using phosphatidylserine-containing fluorescent bioparticles. The pro-inflammatory activation of microglia was assessed via CD11b immunoreactivity and the production of tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6), interleukin-1β (IL-1β) and nitric oxide (NO) via the enzyme-linked immunosorbent assay or the Griess test. We evaluated the ability of curcumin to ameliorate the phagocytic ability of EMF-exposed N9 cells, including checking the expression of MFG-E8, αvβ3 integrin, TLR4, nuclear factor-κB (NF-κB) and signal transducer and activator of transcription 3 (STAT3) using Western blotting.ResultsEMF exposure dramatically enhanced the expression of CD11b and depressed the phagocytic ability of N9 cells. rmMFG-E8 could clearly ameliorate the phagocytic ability of N9 cells after EMF exposure. We also found that EMF exposure significantly increased the secretion of pro-inflammatory cytokines (TNF-α, IL-6 and IL-1β) and the production of NO; however, these increases were efficiently chilled by the addition of curcumin to the culture medium. This reduction led to the amelioration of the phagocytic ability of EMF-exposed N9 cells. Western blot analysis revealed that curcumin and naloxone restored the expression of MFG-E8 but had no effect on TLR4 and cytosolic STAT3. Moreover, curcumin significantly reduced the expression of NF-κB p65 in nuclei and phospho-STAT3 (p-STAT3) in cytosols and nuclei.ConclusionsThis study indicates that curcumin ameliorates the depressed MFG-E8 expression and the attenuated phagocytic ability of EMF-exposed N9 cells, which is attributable to the inhibition of the pro-inflammatory response through the NF-κB and STAT3 pathways.

TREM2 Regulates Heat Acclimation-Induced Microglial M2 Polarization Involving the PI3K-Akt Pathway Following EMF Exposure

“…In the present study, we observed pro-inflammatory M1 activation and a significant decrease in the microglial M2 phenotype in N9 cells after EMF exposure. These findings are consistent with our previous data, which indicated a pro-inflammatory response and a decrease in phagocytosis in EMF-treated N9 cells (He et al, 2014). Notably, as a beneficial intervention, HA treatment significantly suppressed the secretion of pro-inflammatory cytokines and the expression of M1 markers and increases the secretion of anti-inflammatory cytokines and the expression of M2 markers in N9 cells 12 h after EMF exposure.…”

“…The 20-min EMF treatment was identified as a threshold condition representing the time of duration beyond which cytotoxicity significantly increases as explained in a previous study (He et al, 2016). In addition, based on the previous time effect experiments of EMF-induced pro-inflammatory responses (Yang et al, 2010;He et al, 2014), the threshold 12-h recovery time after EMF exposure with prominent pro-inflammatory activity was employed in the present study. Clearly, ELISA detection indicated that EMF exposure resulted in increased levels of TNF-α ( Figure 1A), IL-1β ( Figure 1B), but not IL-6 ( Figure 1C), and decreased levels of IL-4 ( Figure 1D) and IL-10 ( Figure 1E).…”

Inhibition of STAT3- and MAPK-dependent PGE2 synthesis ameliorates phagocytosis of fibrillar β-amyloid peptide (1-42) via EP2 receptor in EMF-stimulated N9 microglial cells

“…In a previous work, we demonstrated that an initial activation and pro-inflammatory response of microglia is induced by EMF exposure [30, 31]. Under the inflammatory conditions, we further observed an alteration in the clearance function of EMF-stimulated N9 cells [9]. Similarly, in this study, we observed an inversed correlation of pro-inflammatory COX-2 and prostaglandin expression with attenuated phagocytosis of 647-fAβ 42 in EMF-stimulated N9 cells.…”

“…Additional evidence has revealed that pro-inflammatory cytokines act selectively to regulate the different types of microglial phagocytosis [8]. We previously observed pro-inflammatory responses and a depression of phagocytic activity in EMF-stimulated N9 microglial cells (N9 cells) [9]. However, it remains a central challenge to determine which special cytokines inhibit microglial Aβ clearance after EMF exposure.…”

Biodegradable micelles enhance the antiglioma activity of curcumin in vitro and in vivo

“…[8][9][10][11][24][25][26][27] It has received extensive attention with its unique effectiveness in glioma therapy. Previous studies demonstrated that Cur can significantly inhibit the proliferation of glioma cells by downregulating multidrug resistance proteins that cause the efflux of many chemotherapeutic agents.…”