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Clinical Rheumatology

, Volume 37, Issue 4, pp 1017–1024 | Cite as

ADAM-17 is expressed in the inflammatory myopathy and is involved with interstitial lung disease

  • Airi Nishimi
  • Takeo Isozaki
  • Shinichiro Nishimi
  • Sho Ishii
  • Takahiro Tokunaga
  • Hidekazu Furuya
  • Kuninobu Wakabayashi
  • Tsuyoshi Kasama
Original Article
  • 135 Downloads

Abstract

The “A disintegrin and metalloprotease” (ADAM) family is thought to play an important role in tissue destruction and inflammatory reactions. ADAM-17 was first described as the protease responsible for tumor necrosis factor (TNF)-α shedding. Here, we have shown the expression of ADAM-17 in inflammatory myopathy and demonstrated the role of inflammation in interstitial lung diseases (ILD). ADAM-17 in inflammatory myopathy serum [polymyositis (n = 26), dermatomyositis (n = 34), and clinically amyopathic dermatomyositis (n = 10)] and healthy control (n = 19) was measured using enzyme-linked immunosorbent assay. The relationship between ADAM-17 and clinical data was examined. Finally, we performed immunohistological analysis to investigate the expression of ADAM-17 on the muscles of the inflammatory myopathy patients. ADAM-17 in inflammatory myopathy was significantly higher than that in healthy control (mean ± SEM, 1048 ± 312 and 36 ± 18 pg/ml, respectively; p < 0.05). ADAM-17 in post-treatment with corticosteroid and/or immunosuppressant serum was significantly decreased compared with that in pre-treatment serum (1465 ± 562 and 1059 ± 503 pg/ml, respectively; p < 0.01). ADAM-17 was significantly positively correlated with fractalkine/CX3CL1 and CXCL16. In addition, ADAM-17 in inflammatory myopathy with ILD patients (n = 46) was significantly higher than that in non-ILD patients (n = 24) (1379 ± 454 and 413 ± 226 pg/ml, respectively; p < 0.05). We found the expression of ADAM-17 on muscle biopsy tissue. ADAM-17 is expressed in inflammatory myopathies especially ILD, suggesting that ADAM-17 plays a role in lung fibrosis. ADAM-17 may be a potential target in inflammatory myopathies with ILD.

Keywords

ADAM-17 CXCL16 Fractalkine/CX3CL1 Inflammatory myopathy Interstitial lung disease 

Abbreviations

ILD

interstitial lung disease

ADAM

A disintegrin and metalloprotease

TNF

tumor necrosis factor

PM

polymyositis

DM

dermatomyositis

CADM

clinically amyopathic dermatomyositis

ADM

amyopathic DM

EAM

experimental autoimmune myositis

HDM

hypomyopathic dermatomyositis

CK

creatine kinase

ELISA

enzyme-linked immunosorbent assay

LDH

lactate dehydrogenase

FBS

fetal bovine serum

PBS

phosphate buffered saline

HLF

human lung fibroblasts

IL-6R

interleukine-6 receptor

RA

rheumatoid arthritis

ST

synovial tissue

OA

osteoarthritis

TACE

tumor-necrosis-factor-converting-enzyme

AREG

amphiregulin

TGF

transforming growth factor

MHC-I

major histocompatibility complex I

IP-10/CXCL10

interferon gamma-induced protein-10/CXCL10

Notes

Acknowledgements

We thank Ms. Takeuchi for performing all ELISAs.

Authors’ contributions

AN performed all assays with assistance from TI, SN, SI, TT, HF, and KW. TI also assisted with the acquisition of data. AN performed the statistical analysis. TI, KW, and TK conceived the study and participated in its design and coordination. TI assisted AN with drafting the manuscript. All authors read and approved the final manuscript.

Compliance with ethical standards

We obtained written informed consent from all patients who enrolled in the study. The study received approval from the Bio-Ethics Committee of the Department of Medicine, Showa University School of Medicine (No. 1892).

Disclosures

None.

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Copyright information

© International League of Associations for Rheumatology (ILAR) 2018

Authors and Affiliations

  • Airi Nishimi
    • 1
  • Takeo Isozaki
    • 1
  • Shinichiro Nishimi
    • 1
  • Sho Ishii
    • 1
  • Takahiro Tokunaga
    • 1
  • Hidekazu Furuya
    • 1
  • Kuninobu Wakabayashi
    • 1
  • Tsuyoshi Kasama
    • 1
  1. 1.Division of Rheumatology, Department of MedicineShowa University School of MedicineTokyoJapan

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