Glutathione Induced Immune-Stimulatory Activity by Promoting M1-Like Macrophages Polarization via Potential ROS Scavenging Capacity

Abstract

The present study investigated the immunomodulatory activity of reduced glutathione (GSH) by assessment of the macrophage polarization (MP)-mediated immune response in RAW 264.7 cells. Furthermore, we identified the signal pathway associated with immune regulation by GSH. The expressions of MP-associated cytokines and chemokines were assessed using cytokine array, nCounter Sprit platform, ELISA and immunoblotting. Phagocytosis activity and intracellular reactive oxygen species (ROS) generation were measured using fluorescence-activated cell sorter. As results of the cytokine array and nCounter gene array, GSH not only up-regulated pro-inflammatory cytokines, including interleukins and tumor necrosis factor-α, but also overexpressed neutrophil-attracting chemokines. Furthermore, GSH significantly stimulated the production of immune mediators, including nitric oxide and PGE2, as well as phagocytosis activity through nuclear factor kappa B activation. In addition, GSH significantly decreased LPS-induced ROS generation, which was associated with an activation of nuclear factor erythroid-derived 2-related factor 2 (Nrf2)/ heme oxygenease-1 (HO-1) signaling pathway. Our results suggest that GSH has potential ROS scavenging capacity via the induction of Nrf2-mediated HO-1, and immune-enhancing activity by regulation of M1-like macrophage polarization, indicating that GSH may be a useful strategy to increase the human defense system.

Glutathione Injection Alleviates the Fluctuation of Metabolic Response under Thermal Stress in Olive Flounder, Paralichthys olivaceus

“…To alleviate oxidative stress, cells possess antioxidant components, including glutathione (glutamyl-cysteinyl-glycine; GSH). GSH works mainly as an antioxidant defense mechanism and is involved in nutrient metabolism, protein synthesis, and the regulation of other cellular events in human and animals [12]. It was confirmed that the inoculation of the vaccine with GSH was effective for the reduction of stress and inflammatory response in calves [13].…”

A Novel Peptide Oligomer of Bacitracin Induces M1 Macrophage Polarization by Facilitating Ca2+ Influx

“…As described previously, the phagocytic activity was measured using a phagocytosis assay kit [ 20 ]. In brief, RAW 264.7 cells were seeded on 6-well plates at a density of 4 × 10 5 cells/well, and incubated for 24 h. The cells were treated with CSP32 and l ng/mL LPS for 24 h, and then, a fluorescently labeled latex bead-rabbit IgG-FITC complex was added for 2 h. The cells were washed and treated with 40 μM DAPI.…”

Resolving Metabolic Heterogeneity in Experimental Models of the Tumor Microenvironment from a Stable Isotope Resolved Metabolomics Perspective

“…Itaconate is known to be elicited by LPS in inflammatory Mφ to inhibit microbial growth [177], but its excess buildup was also shown to be anti-inflammatory [178,179]. GSH has been shown to stimulate pro-inflammatory activity while relieving oxidative stress in RAW 264.7 macrophages [180]. Moreover, we saw multiple CM-dependent changes in the Krebs cycle, notably the enhanced buildup of both unlabeled and 13 C-itaconate (g') as well as the less blocked Krebs cycle in M1-Mφ as evidenced by the less depletion of 13 C labeled Krebs cycle products (a', c', and d') relative to M2-Mφ.…”