Placenta Specific 8 Suppresses IL-18 Production through Regulation of Autophagy and Is Associated with Adult Still Disease
| العنوان: | Placenta Specific 8 Suppresses IL-18 Production through Regulation of Autophagy and Is Associated with Adult Still Disease |
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| المؤلفون: | Masahiro Yokosawa, Kotona Furuyama, Seiji Segawa, Yuya Kondo, Daisuke Goto, Hiroto Tsuboi, Yuji Nakai, Isao Matsumoto, Takayuki Sumida, Shunta Kaneko, Akira Iizuka |
| المصدر: | The Journal of Immunology. 201:3534-3545 |
| بيانات النشر: | The American Association of Immunologists, 2018. |
| سنة النشر: | 2018 |
| مصطلحات موضوعية: | Adult, 0301 basic medicine, Fever, THP-1 Cells, Interleukin-1beta, Immunology, Arthritis, Stimulation, Monocytes, Pathogenesis, 03 medical and health sciences, 0302 clinical medicine, Downregulation and upregulation, Autophagy, medicine, Humans, Immunology and Allergy, THP1 cell line, Oligonucleotide Array Sequence Analysis, 030203 arthritis & rheumatology, biology, business.industry, Interleukin-18, Proteins, Exanthema, medicine.disease, Ferritin, 030104 developmental biology, Ferritins, biology.protein, Interleukin 18, business, Still's Disease, Adult-Onset, Biomarkers |
| الوصف: | Adult Still disease (ASD) is a systemic disorder of unknown etiology characterized by high spiking fever, rash, and arthritis. The purpose of this study was to identify genes specifically associated with the active phase of the disease. In this study, we have reported that placenta specific 8 (PLAC8) was a newly specific gene involved in ASD. DNA microarray and validation analysis using human monocytes revealed that the expression of PLAC8 was significantly higher in active-ASD patients than in inactive-ASD patients and healthy controls. In ASD, PLAC8 expression level correlated with serum levels of CRP, ferritin, IL-1β, and IL-18. Stimulation of monocytes with LPS results in PLAC8 upregulation. LPS or nigericin stimulation of PLAC8-overexpressing human monocytic cell line (THP-1), but not mock THP-1 cells, was associated with a significant decrease in IL-1β and IL-18 production. PLAC8 overexpression in THP-1 cells was associated with enhanced autophagy and suppression of IL-1β and IL-18 production. Therefore, we found that PLAC8 was upregulated in activated monocytes, as was IL-1β and IL-18. The upregulated PLAC8 acts on the synthesis of inactive precursors of IL-1β and IL-18 and seemed to suppress the production of IL-1β and IL-18 by negative feedback through enhanced autophagy, resulting in the suppression of ASD. The results highlight the role of PLAC8 in the pathogenesis of ASD and suggest its potential suitability as an activity marker and therapeutic target in ASD. |
| تدمد: | 1550-6606 0022-1767 |
| الوصول الحر: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::db1ebca7ecb3bc0e008946d49585b6caTest https://doi.org/10.4049/jimmunol.1800667Test |
| حقوق: | OPEN |
| رقم الانضمام: | edsair.doi.dedup.....db1ebca7ecb3bc0e008946d49585b6ca |
| قاعدة البيانات: | OpenAIRE |
| تدمد: | 15506606 00221767 |
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