Immune modulatory effect of a pure compound Isolated from Taxillus lonicerifolius var. lonicerifolius in murine model of asthma

Allergic asthma is one of the most important Th2 lymphocyte-mediated chronic inflammatory airway disease worldwide, both in the developing and developed countries. In the patients of allergic asthma, it is well characterized by skewed polarization of helper T cell development toward type 2 T helper cell with increased production of interleukin 4 (IL-4) and IL-5. Asthma is characterized by airway eosinophils inflammation, mucus hypersecretion, bronchial hyperreactivity, the presence of high levels of allergen-specific IgE. There is strong evidence for the therapeutic effect of type 1 T helper-related cytokines or reagents, such as IFN-α, IFN-γ, IL-12 or CpG-motif oligodexynucleotide on airway inflammation. Dendritic cell are the most potent antigen presenting cells for priming the naïve T helper cells. Taxillus lonicerifolius var. lonicerifolius is one species of Loranthaceae in Taiwan. One pure compound (1400041), kindly providing by Pro. Leu,. isolated from the fresh T. lonicerifolius var. lonicerifolius was used in this study. In this study, we found stimulating BM-DC with 30μg/ml 1400041 could enhance production of IL-12 p40, IL-12 p70 and IL-10, as well as enhance cell surface expression of CD80 (B7.1), CD86 (B7.2), MHCI and MHCII molecule. In addition, the capacity for endocytosis was suppressed in BM-DC treated with 1400041. And, neutralization with antibody against Toll-like receptor（TLR）-4 inhibited the 1400041-induced production of IL-12 p40, suggest a crucial role for TLR-4 in signaling DC upon incubation with 1400041. In addition, treatment of BM-DC with 1400041 resulted in enhanced T cell-stimulatory capacity and increased T cell secretion of IFN-γ. Taken together, our in vitro data demonstrated that this 1400041 can effectively promote the activation and maturation of DC, suggesting that 1400041 may possess a potential in regulating immune responses. To test the effect of 1400041 in vivo, we further examined the effects of this compound on antigen-specific antibody and cytokine production. Immunization with ovalbumin (OVA) / 1400041 showed that the anti-OVA IgG2a levels were significantly increased and the anti-OVA IgE levels were significantly decreased compared with that of OVA-alone group. While 1400041 had no significantly effect on the anti-OVA IgG1 levels and induced the secretion of IFN-g, it inhibited the secretion of IL-4 and IL-5. The findings demonstrate that 1400041 could be used as adjuvant to induce Th1 immunity in BALB/c mice. In the future, we aim to study the therapeutic effect and immune modulatory mechanism of 1400041 in murine model of asthma. We expect this compound might be used as novel therapeutic reagent for asthma treatment.