Macrophage immunomodulatory effects of low molecular weight peptides from Mytilus coruscus via NF-κB/MAPK signaling pathways

Abstract

• MCP induced the activation of RAW264.7 macrophages and strengthened the phagocytosis of macrophages. • MCP significantly promoted the generation of ROS, NO and pro-inflammatory factors. • MCP activated macrophages via NF-κB/MAPK signaling pathways. • MCP may serve as a promising immunomodulator. The objective of the study was to investigate the immunomodulatory activity of the low molecular weight peptides (<1 kDa, named MCP) from thick shell mussel ( Mytilus coruscus ) protein hydrolysates with proliferation promotion effect on RAW264.7 macrophages. The evaluation of LDH leakage revealed no cytotoxicity of MCP on RAW264.7 macrophages. Additionally, the cell morphology changes and ACP level detection showed that cells were in an activated condition. Inflammatory mediator tests indicated that MCP could significantly induce NO and ROS production, and promote the phagocytosis of RAW264.7 macrophages. It also significantly increased the secretion of pro-inflammatory cytokines IL-6, IL-1β, TNF-α, and IFN-γ. Furthermore, MCP promoted IκB-α phosphorylation and ubiquitination, NF-κB p65 activation and nuclear translocation, JNK, ERK, and p38 kinases phosphorylation of MAPK pathways, thereby regulating the secretion of inflammatory mediators. These findings proved that the immunomodulatory activities were possessed by MCP on RAW264.7 macrophages via the NF-κB and MAPKs signaling pathways. Therefore, MCP can be developed as a potential functional food or nutraceutical.