Immunomodulatory Properties of Polysaccharides from the Coral Pseudopterogorgia americana in Macrophages

Polysaccharides from marine organisms produce an important regulatory effect on the mammalian immune system. In this study, the immunomodulatory properties of a polysaccharide that was isolated from the coral Pseudopterogorgia americana (PPA) were investigated. PPA increased the expression levels of tumour necrosis factor-alpha (TNF-alpha), interleukin-6 (IL-6) and cyclooxygenase-2 (COX-2), but not inducible nitric oxide synthase and nitric oxide, in macrophages. A mechanistic study revealed that PPA activated macrophages through the toll-like receptor-4 and induced the generation of reactive oxygen species (ROS), increased the phosphorylation levels of protein kinase C (PKC)-alpha, PKC-delta and mitogen-activated protein kinases (MAPK), and activated NF-kappa B. The inhibition of ROS and knockdown of PKC-alpha reduced PPA-mediated TNF-alpha and IL-6 expression; however, the knockdown of PKC-delta significantly increased PPA-mediated TNF-alpha expression. In addition, the inhibition of c-Jun N-terminal kinase-1/2 and NF-kappa B reduced PPA-mediated TNF-alpha, IL-6 and COX-2 expression. Furthermore, the inhibition of ROS, MAPK and PKC-alpha/delta reduced PPA-mediated NF-kappa B activation, indicating that ROS, MAPK and PKC-alpha/delta function as upstream signals of NF-kappa B. Finally, PPA treatment decreased the phagocytosis activity of macrophages and reduced cytokine expression in bacteria-infected macrophages. Taken together, our current findings suggest that PPA can potentially play a role in the development of immune modulators in the future.