A Novel Phycobiliprotein Alleviates Allergic Airway Inflammation by Modulating Immune Responses

Rationale: It has been claimed that phycocyanin exhibits pharmaceutical functions in inhibiting histamine release and leukotriene biosynthesis. In allergic asthma, these inflammatory mediators are crucial for disease progression. Objectives: The aim of this study was to evaluate the therapeutic potential of R-phycocyanin (R-PC) against allergic airway inflammation. Methods: Mouse bone marrow-derived dendritic cells (BMDCs) were used to evaluate the immunomodulatory functions of R-PC. In addition, an airway inflammatory model was used to evaluate the therapeutic potential of R-PC. Measurements and Main Results: R-PC treatment resulted in a decrease of endocytosis, increase of costimulatory molecule expression, and enhancement of interleukin-12 production in mouse BMDCs. Moreover, R-PC-treated cultured dendritic cells were able to promote CD4(+) T-cell stimulatory capacity and increase interferon-gamma expression in CD4+ T cells. Intraperitoneal administration of R-PC suppressed ovalbumin (OVA)-induced airway hyperresponsiveness, serum levels of OVA-specific IgE and IgG1, eosinophil infiltration, Th2 cytokine levels, and eotaxin in bronchoalveolar lavage fluid of mice. Antibody against Toll-like receptor-4 was able to inhibit R-PC-induced IL-12 p70 production. Moreover, inhibition of nuclear factor-kappa B (NF-kappa B) by helenalin and inhibition of the JNK pathway by JNK inhibitor II inhibited R-PC-induced IL-12 p70 production. Western blotting and electrophoretic mobility shift assays showed that R-PC augmented phosphorylation of the inhibitors of NF-kappa B and inhibitors of NF-kappa B kinase and facilitated NF-kappa B activity. Conclusions: Our data demonstrated that R-PC promoted activation and maturation of cultured dendritic cells and skewed the immunological function toward Th1 activity. Therefore, R-PC may have potential in regulating immune responses and application in reducing allergic asthma.