The Role of Autophagy in Rheumatic Disease

Feng, Yong; Li, Bo; Li, Xue Yi; Wu, Zhen

doi:10.2174/1389450117666160819155028

Cited by 22 publications

(12 citation statements)

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“…We enrolled a limited number of patients with active RA who were followed throughout 6-month therapies. Because the medications used, such as corticosteroids, may influence autophagy through downregulating proinflammatory cytokine secretion [ 44 ], their interference should be considered. In contrast to the results of a previous report in an early RA cohort [ 45 ], we did not reveal a significant association between autophagy expression and ACPA levels in patients with RA.…”

Section: Discussionmentioning

confidence: 99%

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Association between autophagy and inflammation in patients with rheumatoid arthritis receiving biologic therapy

et al. 2018

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BackgroundIncreasing evidence indicates a pathogenic role of deregulated autophagy in rheumatoid arthritis (RA). We examined the relationship between autophagy and inflammatory parameters in patients with RA receiving biologic therapy.MethodsIn 72 patients with RA and 20 healthy control subjects (HC), autophagosome levels were determined by the mean fluorescence intensity (MFI) of autophagosomotropic dye incorporated into circulating immune cells, and p62 expression levels in immune cells were measured by flow cytometry. We used immunoblotting to examine protein expression of LC3-II and p62 in peripheral blood mononuclear cells.ResultsPatients with RA had significantly higher levels of autophagosome reflected by MFI of Cyto-ID in circulating lymphocytes, monocytes, and granulocytes (median values, 3.6, 11.6, and 64.8, respectively) compared with HC (1.9, 6.0, and 35.8; respectively) (all p < 0.001). p62 MFI levels in lymphocytes and granulocytes from patients with RA (17.1 and 8.6, respectively) were significantly lower than those in the corresponding cells from HC (20.2, p < 0.05; and 13.1, p < 0.001, respectively). Significantly higher levels of LC3-II protein expression in contrast to lower p62 protein levels were observed in patients with RA than in HC. The autophagosome levels in immune cells were significantly correlated with inflammatory parameters in patients with RA, and they were significantly decreased with disease remission after treatment with tumor necrosis factor-α inhibitors or interleukin-6 receptor inhibitor.ConclusionsElevated autophagy with significant correlation to inflammation suggests the involvement of autophagy in RA pathogenesis. The effectiveness of biologic therapy might be partly related to the downregulation of autophagy expression.Electronic supplementary materialThe online version of this article (10.1186/s13075-018-1763-0) contains supplementary material, which is available to authorized users.

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Section: Discussionmentioning

confidence: 99%

“…Our preliminary results also indicated that the therapeutic effectiveness of biologics may be related at least in part to their downregulation of autophagy expression. The elucidation of the pathogenic role of autophagy in RA may allow for the development of novel pharmaceutical agents in the future [ 44 , 48 ].…”

Section: Discussionmentioning

confidence: 99%

Association between autophagy and inflammation in patients with rheumatoid arthritis receiving biologic therapy

et al. 2018

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“…The absence of a significant effect of 3-methyladenine might be related to the small number of the enrolled AOSD patients or the dual role of 3-methyladenine in the modulation of autophagy [ 37 ]. Medications, such as corticosteroids, may influence autophagy by reducing cytokine secretion [ 38 ] and drug interference should be considered. Further studies are needed to elucidate the mechanism of impaired autophagy flux in AOSD.…”

Section: Discussionmentioning

confidence: 99%

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

et al. 2017

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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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“…Autophagy plays an important role in homeostasis, mediating the digestion and recycling of cytoplasmic organelles, proteins and macromolecules (Feng et al 2018). The generation of autophagosomes is a hallmark of autophagy (Mizushima 2007).…”

Section: Discussionmentioning

confidence: 99%

Oridonin suppresses autophagy and survival in rheumatoid arthritis fibroblast-like synoviocytes

Huang

Zhu

et al. 2020

Pharmaceutical Biology

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Context: Oridonin exhibits various pharmacological and physiological activities, including antioxidant, antibacterial, anti-inflammatory, pro-apoptotic, anticancer and neurological effects. However, its role in rheumatoid arthritis (RA) is yet to be revealed. Objective: We evaluated the effects of oridonin on the survival and autophagy of RA-fibroblast-like synoviocytes (FLSs). Materials and methods: RA-FLSs were treated with oridonin at serial concentrations of 0, 2, 4, 6, 8 and 10 mg/mL for 24, 48 and 72 h. Then, cell proliferation and apoptosis were measured. A GFP-LC3 plasmid was transfected into the cells to determine autophagy. Results: Oridonin suppressed RA-FLS proliferation in a dose-dependent manner. The half maximal inhibitory concentrations (IC 50) of oridonin at 24, 48 and 72 h were 8.28, 7.88 and 8.35 mg/mL, respectively. Treatment with oridonin for 24 h increased apoptosis by 4.1%, and increased the protein levels of Bax and cleaved caspase-3 but significantly decreased the levels of IL-1b in the culture supernatant (p < 0.05). In addition, 6 h of oridonin treatment significantly decreased the number of GFP-LC3 punctate dots and inhibited the protein levels of ATG5 and Beclin1 by 80.01% and 42.12%, respectively. Chloroquine (CQ) significantly reinforced the effects of oridonin on inhibition of autophagy, suppression of proliferation, and induction of apoptosis in RA-FLSs (p < 0.05). Conclusions: Our results indicate that treatment with oridonin in combination with CQ inhibits autophagy and cell proliferation and induces apoptosis in RA-FLSs more effectively than treatment oridonin alone. This finding indicates that oridonin is a potential therapeutic agent for RA.

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The Role of Autophagy in Rheumatic Disease

Cited by 22 publications

References 0 publications

Association between autophagy and inflammation in patients with rheumatoid arthritis receiving biologic therapy

Association between autophagy and inflammation in patients with rheumatoid arthritis receiving biologic therapy

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

Oridonin suppresses autophagy and survival in rheumatoid arthritis fibroblast-like synoviocytes

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