laminaran and Dermatitis--Contact

The anti-inflammatory effect on contact dermatitis of the water solubilized 1'-Acetoxychavicol Acetate (ACA) by complexation with β-1,3-glucan isolated form Aureobasidium pullulans black yeast is reported. It is well-known that ACA possesses a function to inhibit the activation of NF-κB by which genes encoding proinflammatory cytokines, chemokines, and growth factors are regulated. However, because ACA is quite insoluble in water, its usefulness has been extremely limited. On the other hand, a triple-helical polysaccharide β-1,3-glucan can include hydrophobic compounds into intrastrand hydrophobic cavity and solubilize poorly water-soluble compounds. In this study, solubilization of ACA by complexation with highly branched β-1,3-glucan was achieved. The effect of anti-inflammatory response of water-soluble ACA complex with β-1,3-glucan was confirmed in vitro and in vivo.

Topics: Animals; Anti-Inflammatory Agents; Benzyl Alcohols; beta-Glucans; Cell Line; Cytokines; Dermatitis, Contact; Dinitrofluorobenzene; Drug Stability; Immunohistochemistry; Inflammation; Lipopolysaccharides; Male; Mice, Inbred BALB C; NF-kappa B; Nitrates; Nitrites; Solubility; Solutions; Tumor Necrosis Factor-alpha; Water

Leukocyte extravasation is initiated by an interaction of selectin adhesion molecules and appropriate carbohydrate ligands. Targeting those interactions seems a promising approach to treat chronic inflammation. We developed a beta-1, 3-glucan sulfate (PS3) with inhibitory activity toward L and P-selectins under static conditions. Here, detailed investigation showed inhibition of P- and L-selectins, but not E-selectin under flow conditions (relative reduction of interaction with appropriate ligands to 34.4+/-16.6, 8.5+/-3.6, or 99.5+/-9.9%, respectively, by PS3 for P-, L- or E-selectin). Intravital microscopy revealed reduction of leukocyte rolling in skin microvasculature from 22.7+/-5.0 to 12.6+/-4.0% after injection of PS3. In the next experiments, mice were sensitized with 2,4,-dinitrofluorobenzene (DNFB), and lymphocytes were transferred into syngeneic recipients, which were challenged by DNFB. Inflammatory responses were reduced when immunity was generated in mice treated with PS3 or in L-selectin-deficient mice. No effect was observed when L-selectin-deficient donor mice were treated with PS3, further suggesting that PS3 acted primarily through inhibition of L-selectin. Elicitation of a contact hypersensitivity response was reduced in P-selectin-deficient and in PS3-treated mice. Again, PS3 had no effect in P-selectin-deficient mice. PS3 is a potent P- and L-selectin inhibitor that may add to the therapy of inflammatory diseases.

Topics: Adoptive Transfer; Allergens; Animals; beta-Glucans; Cell Communication; Cells, Cultured; Dermatitis, Contact; Dinitrofluorobenzene; Disease Models, Animal; Endothelium, Vascular; Glucans; Humans; L-Selectin; Leukocytes, Mononuclear; Male; Mice; Mice, Inbred C57BL; P-Selectin