Astaxanthin treatment reduced oxidative induced pro-inflammatory cytokines secretion in U937: SHP-1 as a novel biological target.
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 (H(2)O(2)), 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 H(2)O(2), (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.
Department of Medicine and Science of Aging, University G. D'Annunzio-Chieti, Chieti 66100, Italy.
Lorenza
L
Speranza
Department of Medicine and Science of Aging, University G. D'Annunzio-Chieti, Chieti 66100, Italy.
Mirko
M
Pesce
Department of Medicine and Science of Aging, University G. D'Annunzio-Chieti, Chieti 66100, Italy.
Antonia
A
Patruno
Department of Medicine and Science of Aging, University G. D'Annunzio-Chieti, Chieti 66100, Italy.
Sara
0000-0002-1580-6520
S
Franceschelli
Department of Medicine and Science of Aging, University G. D'Annunzio-Chieti, Chieti 66100, Italy.
Maria Anna de
MA
Lutiis
Department of Medicine and Science of Aging, University G. D'Annunzio-Chieti, Chieti 66100, Italy.
Alfredo
A
Grilli
Department of Medicine and Science of Aging, University G. D'Annunzio-Chieti, Chieti 66100, Italy.
Mario
M
Felaco
D000975:Antioxidants / Q000494:pharmacology; D002338:Carotenoids / Q000494:pharmacology; D002470:Cell Survival / Q000187:drug effects; D002478:Cells, Cultured; D016207:Cytokines / Q000378:metabolism*; D006801:Humans; D006861:Hydrogen Peroxide / Q000378:metabolism; D007249:Inflammation / Q000188:drug therapy* / Q000378:metabolism*; D053583:Interleukin-1beta / Q000378:metabolism; D015850:Interleukin-6 / Q000378:metabolism; D016328:NF-kappa B / Q000378:metabolism; D018384:Oxidative Stress / Q000187:drug effects*; D053824:Protein Tyrosine Phosphatase, Non-Receptor Type 6 / Q000378:metabolism*; D017027:Protein Tyrosine Phosphatases / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism; D020298:U937 Cells; D024341:Xanthophylls / Q000494:pharmacology
D000975:Antioxidants; D016207:Cytokines; D053583:Interleukin-1beta; D015850:Interleukin-6; D016328:NF-kappa B; D014409:Tumor Necrosis Factor-alpha; D024341:Xanthophylls; D002338:Carotenoids; C005948:astaxanthine; D006861:Hydrogen Peroxide; C509249:PTPN6 protein, human; D053824:Protein Tyrosine Phosphatase, Non-Receptor Type 6; D017027:Protein Tyrosine Phosphatases