Lipopolysaccharide induces autophagy by targeting the AMPK-mTOR pathway in Human Nasal Epithelial Cells

Wang, Xuehai; Zhang, Zhonghua; Cai, Xiaolan; Feng, Xin; Liu, Tingting; Li, Xuezhong

doi:10.1016/j.biopha.2017.12.011

Cited by 14 publications

(21 citation statements)

References 34 publications

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“…notably, the lPS concentration and its apoptosis induction rate were found to be negatively related, in contrast with other studies (12,24). A previous study showed that no significant survival inhibition was observed after nasal epithelial cells were treated with a high dose of lPS, which was demonstrated to be the autophagy activator (25). Hence, it was hypothesized that the negative relationship between lPS concentration and survival inhibition could have been caused by autophagy initiated by a higher dose of lPS.…”

Section: Discussioncontrasting

confidence: 80%

Gene expression profile of lipopolysaccharide‑induced apoptosis of nucleus pulposus cells reversed by syringic acid

et al. 2020

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apoptosis of nucleus pulposus (nP) cells has an important role in the process of intervertebral disc degeneration (idd), and the search for novel compounds to prevent apoptosis from occurring is urgently required. in the present study, syringic acid (Syra) was found to exhibit no cytotoxicity on nP cells, and was able to reverse the cytotoxicity, as well as the abnormal expression of Bcl-2 and caspase-3, that were induced by lipopolysaccharide (lPS). The transcriptomes of each group were then analyzed using rna-Seq. a total of 65 differentially expressed genes (deGs) were identified in LPS-stimulated groups (lPS group vs. control group), 819 DEGs were identified in the SyrA-reversed groups (Syra plus lPS group vs. lPS group), and a further 25 deGs were identified in the Syra plus lPS group compared with the control group. reverse transcription-quantitative Pcr validation indicated that the alterations in expression of uroplakin 3B-like 1 (uPK3Bl1), voltage-dependent calcium channel subunit α-2/δ-1 (cacna2d1) and polo-like kinase 4 (PlK4) were consistent with the corresponding results of rna-Seq, and that these genes were involved in both lPS-stimulation and Syra-reversion processes. Kyoto encyclopedia of Genes and Genomes analyses indicated that the deGs in Syra-reversed groups were involved in, amongst other pathways, 'autophagy-other' and 'apoptosis-multiple species'. in conclusion, the addition of Syra to the nP cells co-incubated with lPS appeared to help prevent the abnormal expression of mrnas and apoptosis that had been identified in nP cells incubated with lPS alone. The potential mechanism underlying the reversion of Syra might be attributed to the regulation of cacna2d1 and PlK4.

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Section: Discussioncontrasting

confidence: 80%

Gene expression profile of lipopolysaccharide‑induced apoptosis of nucleus pulposus cells reversed by syringic acid

et al. 2020

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“…LPS activates inflammatory signaling pathways mainly through the classic Toll-like receptor 4 (TLR4) receptor on the cell surface, stimulating the body to produce inflammatory factors, and leading to tissue remodeling. [28][29][30] In addition, LPS can also promote inflammatory responses through other pathways. For example, nasal instillation of LPS in normal people can recruit neutrophils, inhibit the apoptosis of neutrophils, and further stimulate neutrophils to release the inflammatory mediator macrophage inflammatory protein-1α.…”

Section: Discussionmentioning

confidence: 99%

Increased lipopolysaccharide content is positively correlated with glucocorticoid receptor‐beta expression in chronic rhinosinusitis with nasal polyps

Wang

Chen

Zhu³

et al. 2020

Immunity Inflam & Disease

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Introduction Chronic rhinosinusitis with nasal polyps (CRSwNP) is a common and frequently occurring disease of the upper respiratory tract. The nasal instillation of the Gram‐negative (G−) bacterial product lipopolysaccharide (LPS) can induce not only acute sinusitis but also the development of CRSwNP in animal models. Nevertheless, the expression and distribution of LPS in patients with CRSwNP have not been investigated. And the study was to investigate the expression of LPS and its relationship with glucocorticoid receptors (GRs) in CRSwNP. Methods Multiple methods, including bacterial culture and immunohistochemistry, were used to detect and analyze nasal bacteria, plasma LPS content, and the levels of LPS and GR‐α/β, cluster of differentiation 68 (CD68), and myeloperoxidase (MPO) expression, as well as their relationship in CRSwNP. Results The number of G− bacteria and Escherichia coli (E. coli) was not significantly different between CRSwNP subjects and the controls. However, the positive rate of LPS was much higher than that of E. coli in CRSwNP subjects and was significantly higher in noneosinophilic CRSwNP subjects than in eosinophilic CRSwNP subjects. Moreover, the LPS levels were positively correlated with GR‐β but not GR‐α expression in CRSwNP. Immunofluorescence assays showed that LPS was mainly detected in CD68+ macrophages and MPO+ neutrophils, in addition to histiocytes, in CRSwNP. Conclusions Persistent LPS in CRSwNP can lead to unresolved mucosal inflammation, eventually leading to tissue remodeling and the development of CRSwNP. Our findings suggest that increased LPS content and possible resistance to glucocorticoids may be one of the important pathogenic mechanisms of G− bacteria in CRSwNP.

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“…Western blot analysis was performed as previously described. 8 The following antibodies were used: LC3B, P62, GAPDH, UVRAG (Cell Signaling Technology; Danvers, MA, USA).…”

Section: Western Blot Analysismentioning

confidence: 99%

“…Experiments were carried out as described previously. 8 Cells were observed with a JEM-1200EX II electron microscope (JEOL; Tokyo, Japan).…”

Section: Transmission Electron Microscopymentioning

confidence: 99%

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<p>Suppressing UVRAG Induces Radiosensitivity by Triggering Lysosomal Membrane Permeabilization in Hypopharyngeal Squamous Cell Carcinoma</p>

Wang

et al. 2020

OTT

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Introduction: Radiotherapy is one of the most important methods in the treatment of patients with hypopharyngeal squamous cell carcinoma (HSCC). However, radioresistance will be developed after repeated irradiation. Among many key factors contributing to radioresistance, enhanced autophagy is recognized as one of the most important. The ultraviolent irradiation resistance-associated gene (UVRAG) is reported to be a crucial gene involved in the process of autophagy. Here, we test whether UVRAG has effect on the radioresistance of HSCC. Methods: HSCC cell line Fadu cells were treated with irradiation to test levels of autophagy. Tumor tissues from primary and recurrent HSCC patients were tested by immunohistochemistry. Then, we knocked down UVRAG to test its role in cell growth and the malignant behaviors. Response of cells to treatment was examined using LDH release assay, immunofluorescence, Western blot analysis and colony formation. Results: We found that irradiation induced autophagy in Fadu cells. Immunohistochemistry of primary and irradiated HSCC tumor tissues showed that UVRAG was upregulated after irradiation treatment. Inhibiting UVRAG with siRNA interfered cell growth, cell cycle, malignant behaviors and autophagic flux in Fadu cells. Knocking down UVRAG increased DNA damage and cell death induced by irradiation. Finally, we found that inhibiting UVRAG induced lysosomal membrane permeabilization, which contributed to radiosensitization of Fadu cells. Conclusion: Our findings supported the oncogenic properties of UVRAG in HSCC and inhibiting UVRAG increased radiosensitivity in HSCC by triggering lysosomal membrane permeabilization. Therefore, UVRAG might be a promising target in the treatment of HSCC.

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Lipopolysaccharide induces autophagy by targeting the AMPK-mTOR pathway in Human Nasal Epithelial Cells

Cited by 14 publications

References 34 publications

Gene expression profile of lipopolysaccharide‑induced apoptosis of nucleus pulposus cells reversed by syringic acid

Gene expression profile of lipopolysaccharide‑induced apoptosis of nucleus pulposus cells reversed by syringic acid

Increased lipopolysaccharide content is positively correlated with glucocorticoid receptor‐beta expression in chronic rhinosinusitis with nasal polyps

<p>Suppressing UVRAG Induces Radiosensitivity by Triggering Lysosomal Membrane Permeabilization in Hypopharyngeal Squamous Cell Carcinoma</p>

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