F-fucoidan from Saccharina japonica is a novel inducer of galectin-9 and exhibits anti-allergic activity

Abstract

Fucoidan is a sulfated polysaccharide from brown sea algae. In the present study, it was demonstrated that oral administration of F-fucoidan from Saccharina japonica possessed anti-allergic effects using the passive cutaneous anaphylaxis reaction, but not by intraperitoneal administration. The inhibitory mechanism was dependent on galectin-9, which belongs to a soluble lectin family that recognizes β-galactoside and prevents IgE binding to mast cells. The anti-allergy properties of F-fucoidan were cancelled by an intravenous dose of anti-galectin-9 antibody or lactose, which bind competitively with galectin-9 before the passive cutaneous anaphylaxis reaction. F-fucoidan increased the expression level of galectin-9 mRNA in intestinal epithelial cells and serum galectin-9 levels. Oral treatment with F-fucoidan suppressed allergic symptoms through the induction of galectin-9. This is the first report that F-fucoidan can induce the secretion of galectin-9.

Keywords: F-fucoidan; allergy; galectin-9.

Fig. 1

Effect of F-fucoidan on ear edema induced by the passive cutaneous anaphylaxis reaction. Mice were administered F-fucoidan orally (100, 200, or 400 µg/day) for 4 days and conducted a passive cutaneous anaphylaxis reaction. Ear edema was evaluated 2 h after antigen challenge. *p<0.05, significantly different from the values of the group that did not receive crude F-fucoidan. Values represent the means ± SE of 3 mice in each group.

Fig. 2

Difference in the pathway of administration of F-fucoidan. Mice were orally (p.o.) or intraperitoneally (i.p.) administered F-fucoidan (200 µg/day) for 4 days and induced allergic symptoms by passive cutaneous anaphylaxis reaction. Ear edema was evaluated 2 h after antigen challenge. *p<0.05. Values represent the means ± SE of 3 mice in each group.

Fig. 3

Increase in galectin-9 in serum of mice administered F-fucoidan. Mice were administered F-fucoidan orally (200 µg/day) for 4 days and induced allergic symptoms by passive cutaneous anaphylaxis reaction. After evaluation of ear edema, blood was collected. Galectin-9 in serum was detected using an anti-mouse galectin-9 antibody.

Fig. 4

Involvement of galectin-9 in the inhibitory effect of F-fucoidan on type I allergy. (A) Mice were administered F-fucoidan orally (200 µg/day) for 4 days and induced allergic symptoms by passive cutaneous anaphylaxis (PCA) reaction. Galectin-9 mRNA expression in intestinal epithelial cells after PCA reaction was measured. (B) Mice were administered F-fucoidan orally (200 µg/day) for 4 days and intravenously injected with anti-galectin-9 antibody or isotype IgG 1 h before PCA reaction. Ear edema was evaluated 2 h after the antigen challenge. *p<0.05, **p<0.01. Values represent the means ± SE of 3 mice in each group.

Fig. 5

Lactose-mediated inhibition of the interaction between galectin-9 and IgE and the effect of F-fucoidan on ear edema induced by IgE/antigen. (A) IgE and galectin-9 reacted with or without lactose, followed by immunoprecipitation with an anti-mouse IgE antibody and western blotting with an anti-mouse galectin-9 antibody. The data are representative of triplicate experiments. (B) Mice were administered F-fucoidan orally (200 µg/day) for 4 days and intravenously injected with lactose or sucrose 10 min before passive cutaneous anaphylaxis reaction. Ear edema measured 2 h after antigen challenge. *p<0.01. Values represent the means ± SE of 3 mice in each group.

Fig. 6

No effect of F-fucoidan on the increase in IgE and IgG₁ induced by ovalbumin injection. Mice were administered F-fucoidan orally (200 µg/day) for 7 days and immunized with ovalbumin (OVA) as described in the Materials and Methods. Amount of total IgE (µg/ml) in serum collected from the tail vein 1 day before injection OVA (A). Serum OVA-specific IgE (ng/ml) (B) and OVA-specific IgG₁ (µg/ml) (C) content on the final day. Values represent the means ± SE of 6–7 mice in each group. U.D. indicates under detection.