Immunomodulatory Function of κ-Carrageenan Oligosaccharides Acting on LPS-Activated Microglial Cells

Abstract

The major neurodegenerative diseases are characterized by increasing of activated-microglial cells and inflammatory cytokines in the central nervous system. Carrageenan extracted from red algae is a kind of polysaccharide with sulfate groups. The oligosaccharides were obtained from carrageenan by enzymatic degradation. To detect the immunomodulatory activity of κ-carrageenan oligosaccharides (KOS) on microglial cells and the relationship to the sulfate group content, the desulfated derivatives of KOS (DSK) were obtained by dimethyl sulfoxide-methanol-pyridine method. KOS was labeled with fluorescein isothiocyanate. The effect of KOS and DSK on lipopolysaccharide (LPS)-activated microglial cells was detected. Hematoxylin-eosin staining and flow cytometric were used to detect the cell viability. The "scratch" migration assay, ornithine analysis and RT-PCR were used to determine the cell migration, arginase and TNF-α released by microglial cells, respectively. The effect of LPS and KOS on microglial cells was determined by flow cytometry and laser scanning confocal microscopy. The results showed that KOS and DSK could inhibit the cell viability, arginase and TNF-α released by LPS-activated microglia cell with concentration dependent manner. But the effect of DSK was weaker than that of KOS. KOS aggregated on the cell surface firstly, and then they enter into the cell to the nucleus, spread over the entire cell finally. But the exist of LPS could prevent the entrance of KOS. It could be concluded that KOS could protect microglial cells from being activated by LPS, and its inhibition function had relationship to the sulfate group content of KOS, while there were competition between LPS and KOS.

Oligosaccharides Derived from Red Seaweed: Production, Properties, and Potential Health and Cosmetic Applications

“…Numerous studies have revealed the inherent beneficial effects of AOS and COS for human health, including prebiotic effects [ 10 , 11 ], immuno-modulatory [ 87 ], anti-inflammation [ 88 ], anti-oxidant [ 6 , 46 ], and anti-tumor [ 89 ] activities. A compilation of some noteworthy observations in this direction is presented in the following paragraphs.…”

“…AOS and COS have a range of immune-modulatory and anti-inflammatory effects in mucosal and metabolic tissues. COS can protect microglial cells from being activated by lipopolysaccharide (LPS), and its inhibitory function is related to the sulfate group content of COS [ 87 ]. Likewise, carrageenan and COS have been reported to stimulate the induction of interleukin (IL)-10 in human and mice blood cells, with COS inducing more IL-10 in vivo than carrageenan [ 93 ].…”

Bioactive Compounds from Macroalgae in the New Millennium: Implications for Neurodegenerative Diseases

“…Besides this, κ-carrageenan has exhibited prominent biological effects, including antitumor [138], antioxidant [139] and anti-inflammatory [140]. Regarding to neurodegenerative diseases, studies have already showed that κ-carrageenan was able to protect microglial cells against LPS toxicity through the reduction of the viability and content of • NO, TNF-α and IL-10 [140,141]. The authors suggested that the protective function of κ-carrageenan was positively correlated to the sulfate group content of the studied oligosaccharides [140,141].…”

“…Regarding to neurodegenerative diseases, studies have already showed that κ-carrageenan was able to protect microglial cells against LPS toxicity through the reduction of the viability and content of • NO, TNF-α and IL-10 [140,141]. The authors suggested that the protective function of κ-carrageenan was positively correlated to the sulfate group content of the studied oligosaccharides [140,141]. Therefore, κ-carrageenan can potentially be used for preventing the neurodegenerative processes of some CNS diseases.…”

λ-Carrageenan P32 Is a Potent Inhibitor of Rabies Virus Infection

“…Carrageenan is an abundant water-soluble sulfated polysaccharide extracted from red algae that has been widely used in the food industry as an emulsifier, stabilizer or thickener due to its physicochemical stability, safety and affordability [ 8 ]. In recent decades, the biological activities of carrageenan have been investigated, including anti-coagulant [ 9 ], anti-tumor [ 10 ], and immunomodulatory activities [ 11 , 12 ]. In addition, carrageenan can inhibit a broad range of DNA viruses [ 13 ] such as papillomavirus [ 14 , 15 ] and herpes simplex virus [ 16 – 18 ].…”