ABSTRACT
BACKGROUND: Ivermectin (IVM) is widely used in both human and veterinary medicine to treat parasitic infections. Recent reports have suggested that IVM could also have anti-inflammatory properties. METHODS: Here, we investigated the activity of IVM in a murine model of atopic dermatitis (AD) induced by repeated exposure to the allergen Dermatophagoides farinae, and in standard cellular immunological assays. RESULTS: Our results show that topical IVM improved allergic skin inflammation by reducing the priming and activation of allergen-specific T cells, as well as the production of inflammatory cytokines. While IVM had no major impact on the functions of dendritic cells in vivo and in vitro, IVM impaired T-cell activation, proliferation, and cytokine production following polyclonal and antigen-specific stimulation. CONCLUSION: Altogether, our results show that IVM is endowed with topical anti-inflammatory properties that could have important applications for the treatment of T-cell-mediated skin inflammatory diseases.
Subject(s)
Allergens/immunology , Dermatitis, Atopic/immunology , Ivermectin/administration & dosage , Administration, Topical , Animals , Antigens, Dermatophagoides/immunology , Cell Line , Cytokines/metabolism , Dendritic Cells/immunology , Dendritic Cells/metabolism , Dermatitis, Atopic/drug therapy , Dermatitis, Atopic/pathology , Disease Models, Animal , Enzyme-Linked Immunospot Assay , Fragile X Mental Retardation Protein/metabolism , Humans , Inflammation Mediators/metabolism , Lymphocyte Activation/immunology , Macrophages/drug effects , Macrophages/immunology , Macrophages/metabolism , Mice , Mice, Knockout , Receptors, Purinergic P2X4/metabolism , T-Lymphocyte Subsets/drug effects , T-Lymphocyte Subsets/immunology , T-Lymphocyte Subsets/metabolismABSTRACT
The total synthesis of tetra(4-carboranylphenyl)porphyrins 4 and 6 and their zinc(II) complexes 5 and 7 are described. These compounds were characterized by analytical and spectroscopic methods and, in the case of 5, by X-ray crystallography. The water-soluble nido-carboranylporphyrins 6 and 7 were found to have low dark toxicity towards V79 hamster lung fibroblast cells, using a clonogenic assay (50% colony survival, CS(50)>300 microM). Upon light activation nido-carboranylporphyrin 6 effectively induced DNA damage in vitro. Two different methods were used to assess the extent of DNA damage: the super-coiled to nicked DNA and the alkaline Comet assay using human leukemia K562 cells. Significant PDT-induced DNA damage was observed for porphyrin 6 using both assays, compared to light-only and porphyrin-only experiments. It is concluded that this type of nido-carboranylporphyrin is a promising sensitizer for both the boron neutron capture therapy and the photodynamic therapy of tumors.
