Astaxanthin Treatment Reduced Oxidative Induced Pro-Inflammatory Cytokines Secretion in U937: SHP-1 as a Novel Biological Target

Abstract

It has been suggested that oxidative stress activates various intracellular signaling pathways leading to secretion of a variety of pro-inflammatory cytokines and chemokines. SHP-1 is a protein tyrosine phosphatase (PTP) which acts as a negative regulator of immune cytokine signaling. However, intracellular hydrogen peroxide (H2O2), generated endogenously upon stimulation and exogenously from environmental oxidants, has been known to be involved in the process of intracellular signaling through inhibiting various PTPs, including SHP-1. In this study, we investigated the potential role of astaxanthin, an antioxidant marine carotenoid, in re-establishing SHP-1 negative regulation on pro-inflammatory cytokines secretion in U-937 cell line stimulated with oxidative stimulus. ELISA measurement suggested that ASTA treatment (10 µM) reduced pro-inflammatory cytokines secretion (IL-1β, IL-6 and TNF-α) induced through H2O2, (100 µM). Furthermore, this property is elicited by restoration of basal SHP-1 protein expression level and reduced NF-κB (p65) nuclear expression, as showed by western blotting experiments.

Astaxanthin Treatment Confers Protection against Oxidative Stress in U937 Cells Stimulated with Lipopolysaccharide Reducing O2− Production

“…An MTT reduction experiment showed that ASTA did not exhibit any cytotoxic effects on U937 cells at concentrations of 10 µM [16]. Hence, for all experiments this concentration of ASTA was employed.…”

β‐carotene attenuates lipopolysaccharide‐induced inflammation via inhibition of the NF‐κB, JAK2/STAT3 and JNK/p38 MAPK signaling pathways in macrophages

“…In our study, LPS treatment increased JAK2, STAT3 phosphorylation in RAW264.7 cells and peritoneal macrophages. SHP-1, acts as a negative regulator, is a tyrosine phosphatase (PTP) and it could negative regulation of cytokine signaling pathway (Speranza et al, 2012). Speranza et al showed that astaxanthin, a carotenoid found in marine animals and vegetables, reduces activation of NF-ĸB induced by F I G U R E 1 Effects of β-carotene on the viability of (a) RAW264.7 cells and (b) peritoneal macrophages.…”

Marine Pharmacology in 2012–2013: Marine Compounds with Antibacterial, Antidiabetic, Antifungal, Anti-Inflammatory, Antiprotozoal, Antituberculosis, and Antiviral Activities; Affecting the Immune and Nervous Systems, and Other Miscellaneous Mechanisms of Action

“…Inhibition of interleukin-12 p40, interleukin-6 (IL-6) and tumor necrosis factor-α (TNF-α) production, as well as concomitant attenuation of the mitogen-activated protein kinase pathways, was observed, leading the authors to conclude that apo-9′-fucoxanthinone may have “potential therapeutic use…for inflammatory disease”. In a detailed mechanistic study, Speranza and colleagues investigated the antioxidant marine carotenoid astaxanthin ( 116 ), showing that it inhibited hydrogen peroxide-stimulated production of pro-inflammatory cytokines IL-1, IL-6 and TNF-α in a human U937 monocytic cell line by selectively restoring physiological levels and function of the tyrosine phosphatase SHP-1, thus proposing that astaxanthin might become a novel agent for the therapy of inflammatory diseases [122]. Johnson and colleagues identified the alkaloids bengamide A and B ( 117 , 118 ) as potent inhibitors of NFκB and LPS-induced expression of cytokines IL-6, TNF-α and chemokine monocyte chemoattractant protein-1 (MCP-1) release from murine RAW 264.7 macrophages, concluding that these compounds may “serve as therapeutic leads for immune disorders involving inflammation” [123].…”