krn-7000 and Hyperplasia

alpha-Galactosylceramide (alpha-GalCer) is a specific ligand of natural killer T cells (NKT cells) that regulates the immune responses such as tumor rejection and autoimmunity by producing interferon (IFN)-gamma and interleukin (IL)-4. However, it has not been determined whether alpha-GalCer-activated NKT cells modulate allergic inflammation. Because alpha-GalCer induces a large amount of IFN-gamma production by NKT cells, we hypothesized that an in vivo administration of alpha-GalCer could inhibit allergic airway inflammation in mice. Strikingly, a single intraperitoneal injection of alpha-GalCer almost completely abrogated an infiltrate with eosinophils in the lung tissue as well as in the bronchoalveolar lavage. This inhibition of allergic inflammation was associated with a significant decrease in the levels of IL-4, IL-5, and IL-13 in bronchoalveolar lavage fluid and in the number of goblet cells. In addition, this ligand significantly inhibited airway hyperresponsiveness to inhaled methacholine and raised the serum levels of ovalbumin-specific IgG2a with a decrease in those of ovalbumin-specific IgE. In IFN-gamma knockout mice, however, alpha-GalCer failed to exert such inhibitory effects in this asthma model. These results indicate that alpha-GalCer prevents allergic airway inflammation possibly through IFN-gamma production by ligand-activated NKT cells, suggesting the potential therapeutic application of alpha-GalCer in asthma.

Topics: Animals; Antigens; Asthma; Bronchoalveolar Lavage Fluid; Cytotoxicity, Immunologic; Disease Models, Animal; Enzyme-Linked Immunosorbent Assay; Galactosylceramides; Goblet Cells; Hyperplasia; Hypersensitivity; Immunoglobulin E; Immunoglobulin G; Inflammation; Interferon-gamma; Killer Cells, Natural; Ligands; Lung; Mice; Mice, Inbred BALB C; Mice, Knockout; Ovalbumin; T-Lymphocytes; Th2 Cells; Time Factors