Abstract
Arctigenin (ARG), one of the most active ingredients abstracted from seeds of Arctium lappa L., has been proved to exert promising biological activities such as immunomodulatory, anti-viral, and anti-cancer etc. However, the mechanism behind its immunomodulatory function still remains elusive to be further investigated. In this study, we found that ARG had no significant effects on the cell proliferation in both porcine alveolar macrophage cell line (3D4/21) and primary porcine derived alveolar macrophage. It remarkably increased the expression and secretion of the two cytokines including tumor necrosis factor-alpha (TNF-α) and transforming growth factor beta1 (TGF-β1) in a dose-dependent manner with the concomitant enhancement of phagocytosis, which are the indicators of macrophage activation. ARG also elevated the intracellular reactive oxygen species (ROS) production by activating NOX2-based NADPH oxidase. Furthermore, inhibition of ROS generation by diphenyliodonium and apocynin significantly suppressed ARG-induced cytokine secretion and phagocytosis increase, indicating the requirement of ROS for the porcine alveolar macrophage activation. In addition, TLR6-My88 excitation, p38 MAPK and ERK1/2 phosphorylation were all involved in the process. As blocking TLR6 receptor dramatically attenuated the NOX2 oxidase activation, cytokine secretion and phagocytosis increase. Inhibiting ROS generation almost abolished p38 and ERK1/2 phosphorylation, and the cytokine secretion could also be remarkably reduced by p38 and ERK1/2 inhibitors (SB203580 and UO126). Our finding gave a new insight of understanding that ARG could improve the immune-function of porcine alveolar macrophages through TLR6-NOX2 oxidase-MAPKs signaling pathway.
Highlights
The immunomodulatory potentials of Chinese traditional medicine are gaining more interest to dip multiple research for prophylactic and therapeutic purposes in complex disorders caused by various etiological factors
ARG could not affect the expression or secretion of IL-10. These results suggested that ARG could induce a specific activation response in both 3D4/21 cell line and primary porcine alveolar macrophage, as the evidenced by the increased cytokine secretion and the phagocytic activity increase
All the results indicated that NOX2 oxidase activation and reactive oxygen species (ROS) generation were required for ARG-induced activation in 3D4/21 macrophages
Summary
The immunomodulatory potentials of Chinese traditional medicine are gaining more interest to dip multiple research for prophylactic and therapeutic purposes in complex disorders caused by various etiological factors. It was found that ARG possesses immunomodulatory effects on macrophages. As reported by Hyam et al (2013), ARG might ameliorate inflammatory diseases, such as colitis in rats, by inhibiting PI3K and polarizing M1 macrophages to M2-like macrophages. ARG was found to alleviate the macrophages recruitment in the tubulointerstitium in a rat model of obstructive nephropathy, accompanied by the downregulation of NF-κB (p65) signal in the nuclear fraction and the decrease of pro-inflammatory mediator gene expression including MCP-1, TNF-α, IL-1β and IFN-γ in macrophages (Li et al, 2017). In most currently available research, ARG has been mainly demonstrated to resist inflammation in vitro and in vivo, the immune regulating effects and mechanism on macrophage in pigs have not been reported
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