Lipophilic fractions from the marine sponge Halichondria sitiens decrease secretion of pro-inflammatory cytokines by dendritic cells and decrease their ability to induce a Th1 type response by allogeneic CD4⁺ T cells

Abstract

Context: Halichondria (Halichondriidae) marine sponges contain components possessing various biological activities, but immunomodulation is not among the ones reported.

Objective: This study evaluated the immunomodulatory effects of fractions/compounds from Halichondria sitiens Schmidt.

Materials and methods: Crude dichloromethane/methanol extracts of H. sitiens were subjected to various chromatographic techniques to obtain fractions/compounds with immunomodulatory activity, using bioassay-guided isolation. The effects of the fractions/compounds were determined by measuring secretion of cytokines and expression of surface molecules by dendritic cells (DCs) and their ability to stimulate and modify cytokine secretion by allogeneic CD4⁺ T cells. The bioactive fractions were chemically analyzed to identify the immunomodulatory constituents by 1D, 2D NMR, and HRMS data.

Results: Several lipophilic fractions from H. sitiens at 10 μg/mL decreased secretion of the pro-inflammatory cytokines IL-12p40 and IL-6 by the DCs, with maximum inhibition being 64% and 25%, respectively. In addition, fractions B3b3F and B3b3J decreased the ability of DCs to induce T cell secretion of IFN-γ. Fraction B3b3 induced morphological changes in DCs, characterized by extreme elongation of dendrites and cell clustering. Chemical screening revealed the presence of glycerides and some minor unknown constituents in the biologically active fractions. One new glyceride, 2,3-dihydroxypropyl 2-methylhexadecanoate (1), was isolated from one fraction and two known compounds, 3-[(1-methoxyhexadecyl)oxy]propane-1,2-diol (2) and monoheptadecanoin (3), were identified in another, but none of them had immunomodulatory activity.

Discussion and conclusions: These results demonstrate that several lipophilic fractions from H. sitiens have anti-inflammatory effects on DCs and decrease their ability to induce a Th1 type immune response.

Keywords:

• Immunomodulation
• anti-inflammatory effects
• natural products

Acknowledgements

The authors thank Dr Sigridur Jonsdottir at University of Iceland and Dr Shuqi Wang at University of Shandong, China, for high-resolution 2D NMR and accurate MS measurements and Prof. Gudmundur G. Haraldsson at the Science Institute, University of Iceland, for providing the compound 3-[(1-methoxyhexadecyl)oxy]propane-1,2-diol.

Disclosure statement

The authors report no conflicts of interest.

Additional information

Funding

This work was supported by the Icelandic Research Fund, The Icelandic Centre for Research [grant number 110403023]; AVS R&D Fund of Ministry of Fisheries and Agriculture in Iceland [grant number R 16 029-14]; Landspitali University Hospital Research Fund; University of Iceland Research Fund; and the Doctoral Grants of The University of Iceland Research Fund.