Abstract
Biopeptides derived from marine species have garnered significant research interest owing to their anti-inflammatory, antibacterial, and anticancer activities. In our previous study, Hydrostatin-SN1, a bioactive peptide extracted from the Hydrophis cyanocinctus venom gland T7 phage display library, demonstrated anti-inflammatory activity in a dextran sulfate sodium-induced murine colitis model. In this study, we investigated the anti-inflammatory activity and the underlying mechanism of Hydrostatin-SN1 in lipopolysaccharide (LPS)-induced bone marrow-derived macrophage (BMDM) cells and interleukin (IL)-10 knockout mice. The results showed that Hydrostatin-SN1 inhibited phosphorylation of JNK, ERK1/2, and p38 and decreased the mRNA expression of tumor necrosis factor-α (TNF-α), IL-6, and IL-1β in LPS-stimulated BMDM cells in a dose-dependent manner. In LPS-induced acute shock model, a significant higher survival rate of Hydrostatin-SN1-treated mice was observed. Furthermore, Hydrostatin-SN1 reduced body weight loss, decreased disease activity index, reduced spleen index, prevented histological injury, and inhibited the expression of IL-β and phosphorylation of JNK, ERK1/2, and p38 in the colon tissue of IL-10 knockout mice. Additionally, the positive expression rate of TNF-α in mice colon was decreased. Overall, our results suggest that Hydrostatin-SN1 has significant anti-inflammatory effects, both in vitro and in vivo.
Highlights
Tumor necrosis factor-a (TNF-a) is a major pro-inflammatory cytokine, mainly expressed by activated macrophages and T lymphocytes, which plays an important role in regulating proinflammatory responses and biological processes (Aggarwal et al, 2012)
The results showed that LPS dramatically enhanced phosphorylation in bone marrow-derived macrophage (BMDM) cells, while Hydrostatin-SN1 significantly inhibited the phosphorylation induced by LPS (Figure 1)
It was observed that Hydrostatin-SN1 with dosage of 80 mm significantly inhibited the expression of tumor necrosis factor-a (TNF-a) (P < 0.001), IL-6 (P < 0.005), and IL-1b (P < 0.001) in BMDM cells after 6 h of incubation (Figures 2A–C)
Summary
Tumor necrosis factor-a (TNF-a) is a major pro-inflammatory cytokine, mainly expressed by activated macrophages and T lymphocytes, which plays an important role in regulating proinflammatory responses and biological processes (Aggarwal et al, 2012). The binding of TNF to TNFR1 mediates the activation of downstream inflammatory signal pathways (Ashkenazi and Dixit, 1998; Ting and Bertrand, 2016). This process is associated with a variety of autoimmune diseases, such as rheumatoid arthritis (RA) and inflammatory bowel disease (IBD) (Ashkenazi and Dixit, 1998; Wajant and Scheurich, 2011; Brenner et al, 2015). There is a need to identify novel agents that can target TNFR1
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