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FRI0015 The effect of cxcl10 blockade in c protein-induced myositis
  1. J. Kim1,
  2. J. Choi2,
  3. S. Chang2,
  4. K. Shin2,
  5. S.-H. Park3,
  6. H. W. Kim2,
  7. H. Oh2,
  8. M. J. Yoon2,
  9. E. Y. Lee2,
  10. E. B. Lee2,
  11. H. Kawachi4,
  12. H. Kohsaka5,
  13. Y.-W. Song2
  1. 1Internal Medicine, Chungnam National University Hospital, Daejeon
  2. 2Internal Medicine
  3. 3Pathology, Seoul Nationa University College of Medicine, Seoul, Korea, Republic Of
  4. 4Cell Biology, Institute of Nephrology, Niigata University Graduate School of Medical and Dental Sciences, Niigata
  5. 5Department of Medicine and Rheumatology, Graduate School, Tokyo Medical and Dental University, Tokyo, Japan

Abstract

Background CXCL10 (also called interferon-γ-inducible protein 10 [IP-10]) is a chemokine that plays a critical role in the infiltration of T cell in autoimmune disease such as RA and SLE. CXCL10 is reported to be expressed in muscle tissue of polymyositis.

Objectives We investigated the role of CXCL10 and the effect of CXCL10 blockade in C protein-induced myositis, an animal model of polymyositis.

Methods C protein-induced myositis model was induced with human skeletal C protein fragment in 8-week-old female C57BL/6 mice. Immunohistochemistry was performed to detect CXCL10 and CXCR3, its receptor in muscle tissue. CXCR3 in mouse splenocyte was investigated by flow cytometry. Migration assay of mouse splenocyte was performed with 5 μm pore transwell system. Mice with C protein-induced myositis were treated with anti-CXCL10 antibody or control IgG 8 days after the induction of myositis and the inflammation in muscle tissue was assessed 3 week after the induction.

Results Immunohistochemistry showed the expression of CXCL10 and CXCR3 in the muscle of C protein-induced myositis. Flow cytometry demonstrated increased CXCR3+CD4+ T cells (normal mice, 14.14%±1.09% vs. C protein-induced myositis, 37.50%±5.63%) and CXCR3+CD8+ T cells (normal mice, 35.55±2.41% vs. C protein-induced myositis, 79.00%±0.89%) in C protein-induced myositis. Moreover, it was showed that IFN-γ+ cells were increased among CXCR3+CD8+ T cells compared to CXCR3-CD8+ T cells (CXCR3+CD8+ T cell, 28.0 ± 4.2% vs. CXCR3-CD8+ T cell, 9.5 ± 1.5%, p = 0.016). Migration of splenocyte was increased in response to CXCL10 (chemotactic index=1.91±0.45). Treatment with anti-CXCL10 antibody (n=10) showed less inflammation score in muscles than treatment with control IgG (n=10; median [range], anti IP-10, 0.75 [0.25-2.00] vs. control IgG, 1.43 [1.125-4.25], p=0.045).

Conclusions CXCL10 was expressed in the inflammation of C protein-induced myositis model and its blockade suppressed inflammation in muscle.

Disclosure of Interest None Declared

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