FRI0015 The effect of cxcl10 blockade in c protein-induced myositis. (23rd January 2014)

• Record Type: Journal Article
• Authors: Kim, J.; Choi, J.; Chang, S.; Shin, K.; Park, S.-H.; Kim, H. W.; Oh, H.; Yoon, M. J.; Lee, E. Y.; Lee, E. B.; Kawachi, H.; Kohsaka, H.; Song, Y.-W.
• Is Part Of: Annals of the rheumatic diseases. Volume 72:Supplement 3(2013)
• Page Start: A373
• Page End: A373
• Publication Date: 2014-01-23
• Subjects: Rheumatism -- Periodicals; 616.723005
• DOI: 10.1136/annrheumdis-2013-eular.1143
• Languages: English
• ISSNs: 0003-4967

Abstract

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