Background/Purpose: A disintegrin and metalloprotesase (ADAM) family is protease that is thought to have an important role in tissue destruction and inflammatory reaction. ADAMs are also involved in the amputation from the cell surface of inflammatory cytokines. ADAM-17 is one of the ADAM family, and is first described as the protease responsible for tumor necrosis factor (TNF)-α shedding. However, the function of ADAM-17 in myositis is unclear. Here, we have shown the expression of ADAM-17 in inflammatory myopathy and demonstrated the role of inflammation in interstitial lung diseases (ILD).

Methods: The serum were collected from the patients who were diagnosed with inflammatory myopathy in Showa University Hospital from 2003 to 2015. Twenty-six patients were diagnosed with polymyositis (PM), 34 patients were diagnosed with dermatomyositis (DM), and 10 patients were diagnosed clinically amyopathic dermatomyositis (CADM). Clinical manifestations and clinical data were also collected. The levels of ADAM-17 in the serum samples were measured using enzyme-linked immunosorbent assay (ELISA). ADAM-17 expression was determined in muscle tissues from DM using immunohistological staining. To determine that the role of lung fibrosis in inflammatory myopathy with ILD, we used human lung fibroblasts (HLF). ADAM-17 expression on HLF was also demonstrated by immunohistrogical staining.

Results: ADAM-17 in inflammatory myopathy was significantly higher than in healthy control (n=19) (mean ± SEM; 1048 ± 312 pg/ml and 36 ± 18 pg/ml, respectively, p<0.05). ADAM-17 in corticosteroid and/or immunosuppressant treatment patient serum was also significantly decreased compared with in pre treatment patient serum (1465 ± 562 pg/ml and 1059 ± 503 pg/ml, respectively, p<0.01). ADAM-17 was significantly positive correlated with fractalkine/CX3CL1 in serum (r=0.27, p<0.05). In addition, ADAM-17 in inflammatory myopathy with ILD patients (n=46) was significantly higher than in non-ILD patients (n=24) (1379 ± 454 pg/ml and 413 ± 226 pg/ml, respectively, p<0.05). Finally, we found the expression of ADAM-17 in muscle biopsy tissue. Hence, ADAM-17 on HLF was expressed by immunohistochemistry. ADAM-17 in IL-6 and IL-6R stimulated HLF was significantly higher compared with non-stimulated HLF (48 ± 6 pg/ml and 0 ± 0 pg/ml, respectively, p<0.05).

Conclusion: ADAM-17 is expressed in inflammatory myopathies especially with ILD and expressed on HLF, suggesting that ADAM-17 may play the role in lung fibrosis. ADAM-17 may be a potential target in inflammatory myopathies with ILD.

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ACR Meeting Abstracts - https://acrabstracts.org/abstract/adam-17-is-expressed-in-the-inflammatory-myopathy-and-is-involved-with-interstitial-lung-disease/