Endogenously oxidized mitochondrial DNA induces in vivo and in vitro inflammatory responses

Journal of Leukocyte Biology

Shahin Hajizadeh¹  Ing-Marie Jonsson¹  Andrej Tarkowski¹  L. Vincent Collins¹  Elisabeth Holme² 

[1] Department of Rheumatology and Inflammation Research, University of Göteborg, Sweden; and Department of Rheumatology and Inflammation Research, University of Göteborg, Sweden; and Department of Rheumatology and Inflammation Research, University of Göteborg, Sweden; and;Department of Clinical Chemistry, Sahlgrenska University Hospital, Göteborg, Sweden Department of Clinical Chemistry, Sahlgrenska University Hospital, Göteborg, Sweden Department of Clinical Chemistry, Sahlgrenska University Hospital, Göteborg, Sweden

关键词: inflammation;    rheumatoid arthritis;    monocytes/macrophages;   

DOI  :  10.1189/jlb.0703328

学科分类：生理学

来源: Federation of American Societies for Experimental Biology

【 摘 要 】

We report that mitochondrial DNA (mtDNA) is inflammatogenic in vitro and in vivo as a result of the presence of unmethylated CpG sequences and its oxidative status. Purified human and murine mtDNAs induced arthritis when injected intra-articularly (i.a.) in mice. Importantly, oligodeoxynucleotide that contained a single oxidatively damaged base also induced arthritis when injected i.a. in mice. In contrast, neither human nor murine nuclear DNA induced inflammation. mtDNA-induced arthritis was neither B cell- nor T cell-dependent but was mediated by monocytes/macrophages. mtDNA-induced nuclear factor-κB stimulation resulted in the production of tumor necrosis factor α, a potent, arthritogenic factor. Finally, extracellular mtDNA was detected in the synovial fluids of rheumatoid arthritis patients but not of control subjects. We conclude that endogenous mtDNA displays inflammatogenic properties as a result of its content of unmethylated CpG motifs and oxidatively damaged adducts.

【 授权许可】

Unknown