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Antioxidants (Basel). 2019 Sep 18;8(9). pii: E413. doi: 10.3390/antiox8090413.

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

Author information

1
Anti-Aging Research Center and Department of Biochemistry, College of Korean Medicine, Dong-eui University, Busan 47340, Korea. 14711@deu.ac.kr.
2
Anti-Aging Research Center and Department of Biochemistry, College of Korean Medicine, Dong-eui University, Busan 47340, Korea. 14769@deu.ac.kr.
3
Department of Molecular Biology, College of Natural Sciences, Dong-eui University, Busan 47340, Korea. parkch@deu.ac.kr.
4
Anti-Aging Research Center and Department of Biochemistry, College of Korean Medicine, Dong-eui University, Busan 47340, Korea. hongsh@deu.ac.kr.
5
Department of Korean Internal Medicine, College of Korean Medicine, Dong-eui University, Busan 47227, Korea. shhong@deu.ac.kr.
6
Department of Marine Life Sciences, School of Marine Biomedical Sciences, Jeju National University, Jeju 63243, Korea. immunkim@jejunu.ac.kr.
7
Department of Parasitology and Genetics, College of Medicine, Kosin University, Busan 49104, Korea. hcha@kosin.ac.kr.
8
Department of Chemistry, College of Natural Sciences, Pusan National University, Busan 46241, Korea. suhkmann@pusan.ac.kr.
9
Department of Biological Sciences, College of Natural Sciences, Pusan National University, Busan 46241, Korea. khs307@pusan.ac.kr.
10
Department of Food and Nutrition, College of Nursing, Healthcare Sciences & Human Ecology, Dong-eui University, Busan 47340, Korea. hhj2001@deu.ac.kr.
11
Anti-Aging Research Center and Department of Biochemistry, College of Korean Medicine, Dong-eui University, Busan 47340, Korea. choiyh@deu.ac.kr.

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.

KEYWORDS:

antioxidant; glutathione; heme oxygenase-1; immune response; inflammatory cytokines; macrophage polarization; reactive oxygen species

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