Format

Send to

Choose Destination
Arthritis Rheum. 2011 Nov;63(11):3575-85. doi: 10.1002/art.30539.

Immunization with DNA topoisomerase I and Freund's complete adjuvant induces skin and lung fibrosis and autoimmunity via interleukin-6 signaling.

Author information

1
Nagasaki University Graduate School of Biomedical Sciences, Nagasaki, Japan.

Abstract

OBJECTIVE:

The presence of anti-DNA topoisomerase I (anti-topo I) antibody correlates positively with disease severity in patients with systemic sclerosis (SSc). However, the role of induction of anti-topo I antibody production and its potential contribution to the pathogenesis of SSc remain unclear. The aim of this study was to examine the role of anti-topo I antibody in the pathogenesis of SSc.

METHODS:

To assess the contribution of anti-topo I antibody to the pathogenetic process, dermal sclerosis, pulmonary fibrosis, and cytokine production were examined in mice treated with topo I and either Freund's complete adjuvant (CFA) or Freund's incomplete adjuvant (IFA).

RESULTS:

Treatment with topo I and CFA, in contrast to treatment with topo I and IFA, induced skin and lung fibrosis with increased interleukin-6 (IL-6), transforming growth factor β1, and IL-17 production and decreased IL-10 production. Anti-topo I antibody levels were greater in mice treated with topo I and CFA than in mice treated with topo I and IFA. Furthermore, treatment with topo I and CFA increased Th2 and Th17 cell frequencies in bronchoalveolar lavage fluid, whereas treatment with topo I and IFA increased Th1 and Treg cell frequencies. Moreover, loss of IL-6 expression ameliorated skin and lung fibrosis, decreased Th2 and Th17 cell frequencies, and increased Th1 and Treg cell frequencies.

CONCLUSION:

This study is the first to show that treatment with topo I and CFA induces SSc-like skin and lung fibrosis and autoimmune abnormalities. We also suggest that IL-6 plays important roles in the development of fibrosis and autoimmune abnormalities in this novel SSc model.

PMID:
21792823
DOI:
10.1002/art.30539
[Indexed for MEDLINE]
Free full text

Supplemental Content

Full text links

Icon for Wiley
Loading ...
Support Center