Unique Cytokine Production Profile Following Stimulation with DNA in Macrophages from NZB/W F1 Mice

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  • Ogawa Yoshiyuki
    Department of Biopharmaceutics and Drug Metabolism, Graduate School of Pharmaceutical Sciences, Kyoto University
  • Yoshinaga Takaharu
    Department of Biopharmaceutics and Drug Metabolism, Graduate School of Pharmaceutical Sciences, Kyoto University
  • Nishikawa Makiya
    Department of Biopharmaceutics and Drug Metabolism, Graduate School of Pharmaceutical Sciences, Kyoto University
  • Takakura Yoshinobu
    Department of Biopharmaceutics and Drug Metabolism, Graduate School of Pharmaceutical Sciences, Kyoto University

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Abstract

Nucleosome is the major autoantigen in systemic lupus erythematosus (SLE). Professional antigen-presenting cells (APCs), such as macrophages (MΦs) and dendritic cells (DCs), play the central roles in the acquisition of Ag-specific immune responses and activation of such APCs is required for the efficient Ag-presentation. Therefore, adjuvant activity of DNA in nucleosomes would cause the prominent effects on the production of anti-nucleosome antibodies. In this study, we report that elicited peritoneal MΦs from New Zealand Black/White F1 (NZB/W) mice showed a unique cytokine production profile following stimulation with DNA. MΦs from 5-week old NZB/W mice produced a higher amount of IL-6 and about a half amount of TNF-α after stimulation with DNA complexed with cationic liposomes compared with those from control ICR mice. These results suggest that MΦs of NZB/W mice have altered responsiveness to DNA and this might elevate the antigenicity of nucleosomes to induce the production of anti-nucleosome antibodies.

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