Heme Oxygenase-1 Mediated Inhibitory Effects of Peptides Derived from Sea Cucumber on Lipopolysaccharides-induced Inflammation in RAW264.7 Macrophages
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Abstract:
The inhibitory effects and mechanisms of peptides from sea cucumber on lipopolysaccharides (LPS)-induced inflammation responses in RAW264.7 murine macrophages were investigated in this study. The inflammation model in RAW264.7 macrophages was established by LPS treatment. The content of nitric oxide generated by inflammatory macrophages was determined using the Griess assay, and the heme oxygenase-1 (HO-1) mRNA expression as well as the mRNA expression of inducible nitric oxide synthase, tumor necrosis factor-α, interleukin-1β (IL-1β), and IL-6 was measured by real-time quantitative polymerase chain reaction. The results showed that the peptides from sea cucumber significantly inhibited LPS-induced NO production by RAW264.7 macrophages in a dose-dependent manner (p < 0.05), inhibited the mRNA expression of tumor necrosis factor-α, IL-1β, IL-6, , and significantly induced HO-1 expression in RAW264.7 macrophages (p < 0.05). These inhibitory effects were partially reversed by co-treatment with zinc (II)-protoporphyrin IX, a specific inhibitor of HO-1. The sea cucumber peptides with anti-inflammatory activity were rich in glycine, glutamic acid, and aspartic acid, and the peptide fraction with a molecular weight ranging from 180 to 1000 u accounted for 72.12%. These results suggest that peptides derived from sea cucumber inhibit inflammation responses in LPS-stimulated RAW264.7 macrophages by up-regulating HO-1 mRNA expression.