Abstract
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-α (TNF-α), 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)-α, PKC-δ and mitogen-activated protein kinases (MAPK), and activated NF-κB. The inhibition of ROS and knockdown of PKC-α reduced PPA-mediated TNF-α and IL-6 expression; however, the knockdown of PKC-δ significantly increased PPA-mediated TNF-α expression. In addition, the inhibition of c-Jun N-terminal kinase-1/2 and NF-κB reduced PPA-mediated TNF-α, IL-6 and COX-2 expression. Furthermore, the inhibition of ROS, MAPK and PKC-α/δ reduced PPA-mediated NF-κB activation, indicating that ROS, MAPK and PKC-α/δ function as upstream signals of NF-κB. 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.
Highlights
IL-1β is produced as an IL-1β precursor by the activated macrophages and its cleavage is caused by caspase-1, which is regulated by the inflammasomes [26]
We found that proIL1β expression was induced in cells treated with 1, 3 and 10 μg/mL of Pseudopterogorgia americana (PPA) (p < 0.001)
pyrrolidine dithiocarbamic acid ammonium salt (PDTC) significantly reduced COX-2 expression in 10 μg/mL of PPA-activated macrophages (p < 0.001) (Figure 7E). These results indicated that NF-κB positively regulated tumour necrosis factor-α (TNF-α), IL-6 and COX-2 expression in PPA-stimulated macrophages
Summary
The ocean is rich in biodiversity and this makes it a very important source for biomedical researchers to develop active substances. The interest is due, first, to the ocean’s high content of biologically active substances, which are effective in the treatment and prevention of multiple diseases. They are used in the food, cosmetic and other industries, and biologically active substances must be extracted from these organisms [1]. Thanks to systematic studies of marine invertebrates (bivalve molluscs, sponges, echinoderms, etc.), multidimensional data have been obtained confirming that marine invertebrates are an important source of polysaccharides or glycoconjugates, which are noncovalently bound complexes comprising a polysaccharide with a protein component
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