Interferon-γ-mediated inhibition of eotaxin generation : a novel mechanism for regulation of eosinophilic inflammation

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Eotaxin is a CC chemokine specifically binds to CC chemokine receptor (CCR)3, which is preferentially expressed on eosinophils. Eotaxin is implicated in pathogenesis of selective accumulation of eosinophils, which is a characteristic aspect of allergic inflammation. We established monoclonal antibodies against eotaxin and developed a high-sensitive ELISA system. Results of our research are follows.1) Interferon-γcompletely attenuates eotaxin generation. (Miyamasu M.et al. Int. Immunol. 11 : 1001-4, 1999)2) Dermal fibroblasts represent a major cellular source of eotaxin. (Miyamasu M.et al. Cytokine 11 : 751-8, 1999)3) Level of eotaxin is increased in association with clinical parameters in induced sputum of asthmatic patients. (Yamada H.et al. Allergy 55 : 1-6, 2000)4) Interferon-γ does not affect stability of eotaxin mRNA, indicating its inhibitory role at post-translational level. (Miyamasu, M.et al. manuscript in preparation)5) Functional eosinophil CXCR4 is inducible in eosinophils under certain conditions. (Nagase et al. J.Immunol. 164 : 5935-43, 2000 ; Nagase et al. J.Allergy Clin. Immunol. 106 : 1132-9, 2000)6) Bronchial epithelium of asthmatics intensely expresses a Th-2 specific chemokine thymus and activation-related chemokine (TARC). (Sekiya T.et al. J.Immunol. 165 : 2205-13, 2000)Our results indicate that eotaxin represents a potential therapeutic target for allergic inflammation. Further study dealing molecular mechanisms underlying interferon-γ-mediated inhibition of eotaxin generation will facilitate the establishment of a novel strategy for treatment of allergic disorders.