Dihydroartemisinin inhibits catabolism in rat chondrocytes by activating autophagy via inhibition of the NF-κB pathway

Jiang, Libo; Meng, Dehua; Lee, Soomin; Liu, Shu-Hao; Xu, Qintong; Wang, Yang; Zhang, Jian

doi:10.1038/srep38979

Cited by 34 publications

(37 citation statements)

References 33 publications

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“…In addition, several groups have reported that the expression of CXCL-1 was increased after ATG5 silencing in chondrocytes, and autophagy can increase the recruitment of PMNs in lung tissue after 3-MA and CQ treatment. 31,32 Consistent with our expectation, the production of CXCL-1 and the recruitment of PMNs were markedly enhanced after autophagy inhibition compared with infected control group, whereas rapamycin treatment reduced the expression of CXCL-1 and the recruitment of PMNs, which suggested that autophagy can reduce the recruitment of PMNs in A. fumigatus keratitis. Interestingly, as we detected the euchromatin fraction of the nucleus and the number of granules per cytoplasm area in corneas of mice by TEM analysis, we observed that the morphology of PMNs was changed in corneas with 3-MA and CQ treatment, indicating that autophagy may play an essential role in activation, differentiation, and antibacterial ability of neutrophil.…”

Section: Discussionsupporting

confidence: 85%

The Role of Autophagy in the Innate Immune Response to Fungal Keratitis Caused by Aspergillus fumigatus Infection

Cui

Lin

et al. 2020

Invest. Ophthalmol. Vis. Sci.

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Citation: Li C, Li C, Lin J, et al. The role of autophagy in the innate immune response to fungal keratitis caused by Aspergillus fumigatus infection. Invest Ophthalmol Vis Sci. 2020;61(2):25. https://doi.org/10.1167/iovs.61.2.25 PURPOSE.To determine the role of autophagy in the innate immune response to fungal keratitis (FK) caused by Aspergillus fumigatus infection. METHODS.Corneal samples obtained from patients and mice with FK were visualized via transmission electron microscopy (TEM). Autophagy-related proteins LC3B-II, Beclin-1, LAMP-1, and p62 in A. fumigatus-infected corneas of C57BL/6 mice were tested by Western blot. After treatment with autophagy inhibitors 3-methyladenine (3-MA), chloroquine (CQ), or inducer rapamycin, autophagy-related proteins were detected by Western blot. Corneas were photographed with slit lamp microscopy and pathological changes were observed by hematoxylin and eosin staining. Polymorphonuclear neutrophilic leukocytes (PMNs) were assessed by immunofluorescent staining and observed under TEM. The levels of CXCL-1, IL-1β, HMGB1, IL-18, TNF-α, and IL-10 were tested by reverse transcription polymerase chain reaction and Western blot. The quantification of fungal loads was detected and photographed. RESULTS.The accumulation of autophagosomes in corneas of patients and mice with FK was observed with TEM. The expression of LC3B-II, Beclin-1, and LAMP-1 was elevated in corneas after fungal infection, whereas p62 was reduced. Treatment with 3-MA or CQ upregulated clinical scores, pathological changes, and the expression of CXCL-1, IL-1β, HMGB1, IL-18, and TNF-α except IL-10. The morphology of PMNs was changed and PMN recruitment was increased in mice corneas treated with 3-MA or CQ, whereas rapamycin reduced the inflammatory response to keratitis. These results were statistically significant. CONCLUSIONS. A. fumigatus infection increases the expression of autophagy in corneas.Autophagy plays an anti-inflammatory role in the innate immune response to A. fumigatus keratitis.

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Section: Discussionsupporting

confidence: 85%

The Role of Autophagy in the Innate Immune Response to Fungal Keratitis Caused by Aspergillus fumigatus Infection

Cui

Lin

et al. 2020

Invest. Ophthalmol. Vis. Sci.

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“…The same effect was also observed in DHA‐treated chondrocytes, in which DHA treatment attenuated TNF‐α‐stimulated nuclear translocation and the degradation of p65 and IκBα, indicating NF‐κB inhibition. This inhibition then resulted in the induction of autophagy by DHA . Furthermore, Hu et al reported that, in many cancer cell types, including RPMI 8226, NB4, HCT116, and HeLa cells, DHA induces autophagy through the inhibition of NF‐κB activity.…”

Section: Signaling Pathways and Cellular Targets Involved In Autophagsupporting

confidence: 62%

“…99,100 DHA treatment leads to the inhibition of NF-κB activity through blocking RelA/p65 translocation to the nucleus and has a significant repressive effect on the phosphorylation and degradation of IκBα in cancer cells. 48,101 The same effect was also observed in DHA-treated chondrocytes, 102 that further stimulated autophagy. 48 Further evidence showed that DHA-induced autophagy sensitizes some chemotherapeutics, highlighting the role of autophagy as the inducer of cancer cell death.…”

Section: The Ampk Pathwaysupporting

confidence: 55%

“…DHA treatment leads to the inhibition of NF‐κB activity through blocking RelA/p65 translocation to the nucleus and has a significant repressive effect on the phosphorylation and degradation of IκBα in cancer cells . The same effect was also observed in DHA‐treated chondrocytes, in which DHA treatment attenuated TNF‐α‐stimulated nuclear translocation and the degradation of p65 and IκBα, indicating NF‐κB inhibition. This inhibition then resulted in the induction of autophagy by DHA .…”

Section: Signaling Pathways and Cellular Targets Involved In Autophagmentioning

confidence: 71%

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Targeting autophagy enhances the anticancer effect of artemisinin and its derivatives

Sun

Yan

Zou

et al. 2019

Medicinal Research Reviews

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Artemisinin and its derivatives, with their outstanding clinical efficacy and safety, represent the most effective and impactful antimalarial drugs. Apart from its antimalarial effect, artemisinin has also been shown to exhibit selective anticancer properties against multiple cancer types both in vitro and in vivo. Specifically, our previous studies highlighted the therapeutic effects of artemisinin on autophagy regulation. Autophagy is a well‐conserved degradative process that recycles cytoplasmic contents and organelles in lysosomes to maintain cellular homeostasis. The deregulation of autophagy is often observed in cancer cells, where it contributes to tumor adaptation to nutrient‐deficient tumor microenvironments. This review discusses recent advances in the anticancer properties of artemisinin and its derivatives via their regulation of autophagy, mitophagy, and ferritinophagy. In particular, we will discuss the mechanisms of artemisinin activation in cancer and novel findings regarding the role of artemisinin in regulating autophagy, which involves changes in multiple signaling pathways. More importantly, with increasing failure rates and the high cost of the development of novel anticancer drugs, the strategy of repurposing traditional therapeutic Chinese medicinal agents such as artemisinin to treat cancer provides a more attractive alternative. We believe that the topics covered here will be important in demonstrating the potential of artemisinin and its derivatives as safe and potent anticancer agents.

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“…The optical density was measured using a SpectraMax 190 microplate reader (Molecular Devices, Sunnyvale, CA) at 450 nm. Cell viability was calculated as previously described …”

Section: Methodsmentioning

confidence: 99%

Diazoxide ameliorates severity of experimental osteoarthritis by activating autophagy via modulation of the osteoarthritis‐related biomarkers

Meng

Shen

et al. 2018

J of Cellular Biochemistry

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Accumulating evidence suggests that autophagy plays a protective role in chondrocytes and prevents cartilage degeneration in osteoarthritis (OA). The objective of this study was to investigate the effect of diazoxide on chondrocyte death and cartilage degeneration and to determine whether these effects are correlated to autophagy in experimental OA. In this study, a cellular OA model was established by stimulating SW1353 cells with interleukin 1β. A rat OA model was generated by transecting the anterior cruciate ligament combined with the resection of the medial menisci, followed by treatment with diazoxide or diazoxide combination with 3-methyladenine. The percentage of viable cells was evaluated using calcein-acetoxymethyl/propidium iodide double staining. The messenger RNA expression levels of collagen type II alpha 1 chain (COL2A1), matrix metalloproteinase 13 (MMP-13), TIMP metallopeptidase inhibitor 1 (TIMP-1), and a disintegrin and metalloproteinase with thrombospondin motifs 5 (ADAMTS5) were determined using quantitative real-time polymerase chain reaction. The cartilage thickness and joint space were evaluated using ultrasound. SW1353 cell degeneration and autophagosomes were observed using transmission electron microscopy. The expression levels of microtubule-associated protein 1 light chain 3 (LC3), beclin-1, P62, COL2A1, and MMP-13 were evaluated using immunofluorescence staining and Western blot analysis. Diazoxide significantly attenuated articular cartilage degeneration and SW1353 cell death in experimental OA. The restoration of autophagy was observed in the diazoxide-treated group. The beneficial effects of diazoxide were markedly blocked by 3-methyladenine. Diazoxide treatment also modulated the expression levels of OA-related biomarkers. These results demonstrated that diazoxide exerted a chondroprotective effect and attenuated cartilage degeneration by restoring autophagy via modulation of OA-related biomarkers in experimental OA. Diazoxide treatment might be a promising therapeutic approach to prevent the development of OA.

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Dihydroartemisinin inhibits catabolism in rat chondrocytes by activating autophagy via inhibition of the NF-κB pathway

Cited by 34 publications

References 33 publications

The Role of Autophagy in the Innate Immune Response to Fungal Keratitis Caused by Aspergillus fumigatus Infection

The Role of Autophagy in the Innate Immune Response to Fungal Keratitis Caused by Aspergillus fumigatus Infection

Targeting autophagy enhances the anticancer effect of artemisinin and its derivatives

Diazoxide ameliorates severity of experimental osteoarthritis by activating autophagy via modulation of the osteoarthritis‐related biomarkers

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