Exopolysaccharide from Paecilomyces lilacinus modulates macrophage activities through the TLR4/NF-[kappa]B/MAPK pathway

Multiple exopolysaccharides (EPSs) have been isolated from various organisms in extreme environments and have yielded a variety of activities. The present study evaluated the immunomodulatory capabilities of an EPS (termed PH-EPS) derived from the fungus Paecilomyces lilacinus PH0016, which was isolated from a tropical and hyperhaline environment in southern China. The macrophage RAW 264.7 cell line was used to investigate the mechanism of PH-EPS-induced macrophage activation. The results indicated that RAW 264.7 macrophages were activated by PH-EPS, in an effect slightly inferior to lipopolysaccharide (LPS), as evidenced by secretion of interleukin (IL)-1[beta], tumor necrosis factor (TNF)-[alpha] and nitric oxide (NO), and by significantly increased phagocytosis in the cells treated with PH-EPS. Nuclear factor (NF)-[kappa]B p65 was significantly translocated into the nucleus in the PH-EPS-treated cells. In addition, expression of inducible NO synthase (iNOS) and I[kappa]B-[alpha] degradation were enhanced in PH-EPS-treated cells. The phosphorylation levels of p38, JNK and ERK were also significantly increased in the PH-EPS-treated cells. Furthermore, IL-1[beta] and TNF-[alpha] production was markedly decreased in PH-EPS-treated cells when the mitogen-activated protein kinase (MAPK) pathways were blocked by the inhibitor Dectin-1 and by antibodies against Toll-like receptor 4 (TLR4). The present results indicated that PH-EPS from Paecilomyces lilacinus possessed the capability of activating RAW 264.7 cells via the TLR4/NF-[kappa]B/MAPKs signaling pathway. Key words: exopolysaccharide, mitogen-activated protein kinases, nuclear factor-[kappa]B, Paecilomyces lilacinus, Toll-like receptors