The features of arthritis induced by CpG motifs in bacterial DNA

Arthritis Rheum. 2000 Feb;43(2):356-64. doi: 10.1002/1529-0131(200002)43:2<356::AID-ANR15>3.0.CO;2-J.

Abstract

Objective: To investigate the features of arthritis induced by bacterial DNA that contain CpG motifs.

Methods: Bacterial DNA originating from Escherichia coli and Staphylococcus aureus or synthetic oligonucleotides containing CpG motifs were injected directly into knee joints of mice. Histopathologic joint damage, antibody levels, cytokine levels, and synovial messenger RNA (mRNA) expression of cytokines and chemokines were assessed.

Results: Histopathologic signs of arthritis were evident within 2 hours and lasted for at least 3 weeks. Nonmethylated CpG motifs were responsible for the induction of arthritis since oligonucleotides containing these motifs triggered arthritis, whereas methylation of these nucleotides abrogated the inflammatory response. Arthritis was characterized by an influx of monocytic, Mac-1+ cells and by a scarcity of T lymphocytes. The disease was characterized locally by mRNA expression of macrophage-derived cytokines (tumor necrosis factor alpha, interleukin-12 [IL-12], IL-1beta) and chemokines (monocyte chemoattractant protein 1, RANTES) in arthritic joints. Systemically, the arthritis was characterized by increased levels of circulating IL-6 and immunoglobulins.

Conclusion: These findings demonstrate that bacterial DNA that contain nonmethylated CpG motifs induces arthritis, suggesting an important pathogenic role for bacterial DNA in septic arthritis.

MeSH terms

  • Animals
  • Arthritis, Infectious / genetics*
  • Autoantibodies / blood
  • Chemokines / genetics
  • CpG Islands / physiology
  • DNA, Bacterial / drug effects
  • Drug Synergism
  • Immunoglobulins / blood
  • Immunohistochemistry
  • Injections, Intra-Articular
  • Interleukin-6 / blood
  • Joints / chemistry
  • Joints / pathology
  • Lipopolysaccharides / pharmacology
  • Macrophages / chemistry
  • Male
  • Mice
  • Mice, Inbred BALB C
  • Mice, Inbred C3H
  • Mice, Inbred C57BL
  • RNA, Messenger / blood
  • Severity of Illness Index
  • Tumor Necrosis Factor-alpha / analysis

Substances

  • Autoantibodies
  • Chemokines
  • DNA, Bacterial
  • Immunoglobulins
  • Interleukin-6
  • Lipopolysaccharides
  • RNA, Messenger
  • Tumor Necrosis Factor-alpha