Oncotarget

Research Papers: Immunology:

Impaired autophagic flux and its related inflammation in patients with adult-onset Still’s disease

Chia-Wei Hsieh, Chun-Yu Chang, Yi-Ming Chen, Hsin-Hua Chen, Wei-Ting Hung, Ning-Rong Gung, Shiow-Jiuan Wey and Der-Yuan Chen _

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Oncotarget. 2018; 9:110-121. https://doi.org/10.18632/oncotarget.23098

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Abstract

Chia-Wei Hsieh1,2, Chun-Yu Chang3, Yi-Ming Chen1,2,3,4, Hsin-Hua Chen1,2,3,4, Wei-Ting Hung2,3,4, Ning-Rong Gung3, Shiow-Jiuan Wey5 and Der-Yuan Chen1,2,3,4

1 Ph.D. Program in Translational Medicine and Rong Hsing Research Center for Translational Medicine, National Chung Hsing University, Taichung, Taiwan

2 Division of Allergy, Immunology and Rheumatology, Taichung Veterans General Hospital, Taichung, Taiwan

3 Department of Medical Education and Research, Taichung Veterans General Hospital, Taichung, Taiwan

4 Faculty of Medicine, National Yang Ming University, Taipei, Taiwan

5 Division of Dermatology, Chung-Shan Medical University Hospital, Taichung, Taiwan

Correspondence to:

Der-Yuan Chen, email:

Shiow-Jiuan Wey, email:

Keywords: autophagy; autophagy-related genes; autophagic flux; inflammation; adult-onset Still’s disease; Immunology

Received: September 16, 2017 Accepted: November 14, 2017 Published: December 11, 2017

Abstract

The pathogenic role of autophagic immune regulation in adult-onset Still’s disease (AOSD) is unclear. We investigated the relative levels of autophagy in AOSD patients and healthy controls, its association with disease activity or course, and the change in autophagy after 6 months of therapy. Autophagosome levels were determined from the mean fluorescence intensity of autophagosomotropic dye incorporated into circulating immune cells. The fluorescent signal from lymphocytes, monocytes, and granulocytes from AOSD patients was greater than from controls. Levels of p62 fluorescence measured using flow cytometry in lymphocytes and granulocytes from AOSD patients was greater than in the corresponding cells from healthy controls. Expression of Atg5 and LC3-II mRNA and protein levels of p62 and LC3-II were elevated in AOSD patients. Moreover, AOSD activity scores correlated positively with autophagosome levels in monocytes and granulocytes, p62 levels in circulating immune cells, and levels of Beclin-1, Atg5, and LC3-II mRNA. Autophagosome levels and Atg mRNA expression decreased with disease remission in AOSD patients. Elevated autophagosome formation and p62 levels suggest impaired autophagic flux in AOSD.


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