Correlation Between the NLRP3 Inflammasome and the Prognosis of Patients With LSCC

Yi, Xue; Du, Huaidong; Tang, Di; Zhang, Duo; Zhou, Jian; Zhai, Changwen; Yuan, Cuncun; Hsueh, Chi‐Yao; Li, Shengjie; Heng, Yu; Tao, Lei; Lu, Liming

doi:10.3389/fonc.2019.00588

Cited by 44 publications

(39 citation statements)

References 27 publications

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“…Moreover, 5-Fluorouracil (5-FU)-based clinical chemotherapy increased the expression and activation of NLRP3 inflammasome in oral squamous cell carcinoma (OSCC) tissues, which then mediated the chemoresistance [40]. Meanwhile, the high expression level of NLRP3 inflammasome suggested poor prognosis in 121 LSCC tumor tissues [41]. Because inflammasome plays duplex roles in cancer development, targeting inflammasome has become a novel strategy for cancer treatment [42].…”

Section: Discussionmentioning

confidence: 99%

RalB degradation by dihydroartemisinin induces autophagy and IFI16/caspase-1 inflammasome depression in the human laryngeal squamous cell carcinoma

Shi

Wang

et al. 2020

Chin Med

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Background: Interferon-inducible 16 (IFI16)/caspase-1 inflammasome activates and secretes IL-1β. However, it is still unclear whether the IFI16 inflammasome is involved in human laryngeal squamous cell carcinoma. Autophagy directly removed inflammasome components and limited early IL-1β production. RalB is required for the crosstalk between inflammasome and autophagy in macrophages. Dihydroartemisinin (DHA), the main derived ingredient of artemisinin, has a variety of biological activities. The mechanism of DHA in regulating the crosstalk between IFI16 inflammasome and autophagy by inhibiting RalB expression was analyzed in order to provide clues for new therapeutic methods in laryngeal cancer. Methods: The expression of IFI16 was analyzed by Oncomine and GEPIA databases and detected by Western blot and immunohistochemistry. The relationship between IFI16 inflammasome and autophagy was investigated by transmission electron microscopy, immunofluorescence assay, etc. in Hep-2, Cal-27 and HeLa cells treated with DHA. The xenograft tumor of hep-2 cell in nude mice were used to assess the effect of DHA on laryngeal cancer. Results: It was reported for the first time in this study that IFI16 was overexpressed and positively correlated with caspase-1 in laryngeal carcinoma tissues. DHA significantly inhibited the activation of inflammasome and reduced IL-1β production in the microenvironment of Hep-2 cell xenograft tumor in nude mice. Mechanistically, we found that DHA degraded RalB, inhibited USP33 expression, and triggered autophagy. Meanwhile, enhanced autophagy can reduce the expression of RalB and USP33. Furthermore, DHA promotes autophagy, which suppresses the activation of IFI16/ caspase-1 inflammasome and IL-1β production. Conclusions: Therefore, our findings demonstrate that DHA may act as a RalB inhibitor to regulate the crosstalk between autophagy and IFI16/caspase-1 inflammasome, which inhibits IL-1β production in tumor microenvironment.

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Section: Discussionmentioning

confidence: 99%

RalB degradation by dihydroartemisinin induces autophagy and IFI16/caspase-1 inflammasome depression in the human laryngeal squamous cell carcinoma

Shi

Wang

et al. 2020

Chin Med

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“…NLRP3 inflammasome activation increases gene expression of IL-1 and IL-6, thereby enhancing production of hs-CRP [ 23 ]. Recently, NLRP3 inflammasome was proposed as a new biomarker of cardiovascular diseases and predictor of hospitalization and death for myocardial injuries [ 25 , 26 ]. MyD88 complex (called myddosome) is another protein regulator of death-like signals in human cells [ 27 ]; it is a putative marker of the incidence and prognosis of cardiovascular diseases and cancer [ 28 ].…”

Section: Introductionmentioning

confidence: 99%

NLRP3 as Putative Marker of Ipilimumab-Induced Cardiotoxicity in the Presence of Hyperglycemia in Estrogen-Responsive and Triple-Negative Breast Cancer Cells

Quagliariello

Laurentiis

Cocco

et al. 2020

IJMS

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Hyperglycemia, obesity and metabolic syndrome are negative prognostic factors in breast cancer patients. Immune checkpoint inhibitors (ICIs) have revolutionized cancer treatment, achieving unprecedented efficacy in multiple malignancies. However, ICIs are associated with immune-related adverse events involving cardiotoxicity. We aimed to study if hyperglycemia could affect ipilimumab-induced anticancer efficacy and enhance its cardiotoxicity. Human cardiomyocytes and estrogen-responsive and triple-negative breast cancer cells (MCF-7 and MDA-MB-231 cell lines) were exposed to ipilimumab under high glucose (25 mM); low glucose (5.5 mM); high glucose and co-administration of SGLT-2 inhibitor (empagliflozin); shifting from high glucose to low glucose. Study of cell viability and the expression of new putative biomarkers of cardiotoxicity and resistance to ICIs (NLRP3, MyD88, cytokines) were quantified through ELISA (Cayman Chemical) methods. Hyperglycemia during treatment with ipilimumab increased cardiotoxicity and reduced mortality of breast cancer cells in a manner that is sensitive to NLRP3. Notably, treatment with ipilimumab and empagliflozin under high glucose or shifting from high glucose to low glucose reduced significantly the magnitude of the effects, increasing responsiveness to ipilimumab and reducing cardiotoxicity. To our knowledge, this is the first evidence that hyperglycemia exacerbates ipilimumab-induced cardiotoxicity and decreases its anticancer efficacy in MCF-7 and MDA-MB-231 cells. This study sets the stage for further tests on other breast cancer cell lines and primary cardiomyocytes and for preclinical trials in mice aimed to decrease glucose through nutritional interventions or administration of gliflozines during treatment with ipilimumab.

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“…In addition, assembled inflammasomes can activate caspase-1 and cause IL-1β to be secreted from cancer cells [40]. [43]. Because inflammasome plays duplex role in cancer development, targeting inflammasome has become a novel strategy for cancer treatment [44].…”

Section: Discussionmentioning

confidence: 99%

RalB degradation by dihydroartemisinin induces autophagy and IFI16/caspase-1 inflammasome depression in the human Laryngeal squamous cell carcinoma

Shi

Wang

et al. 2020

Preprint

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Background Interferon-inducible 16 (IFI16) /caspase-1 inflammasome activates and secretes IL-1β. However, whether the IFI16 inflammasome involved in human Laryngeal squamous cell carcinoma is still unclear. Autophagy directly removed inflammasome components and limited early IL-1β production. RalB is required for the crosstalk between inflammasome and autophagy in macrophages. Dihydroartemisinin (DHA), the main derived ingredient of artemisinin, has a variety of biological activities. The mechanism of DHA in regulation the crosstalk between IFI16 inflammasome and autophagy by inhibiting RalB expression was analyzed in order to provide clues for new therapeutic methods in laryngeal cancer. Methods The expression of IFI16 was analyzed by Oncomine and GEPIA databases and detected by Western blot and immunohistochemistry. The relationship between IFI16 inflammasome and autophagy was investigated by transmission electron microscopy, immunofluorescence assay, etc. in Hep-2, Cal-27 and HeLa cells with DHA treatment. Hep-2 cell xenograft tumor in nude mice were used to assess the effect of DHA on laryngeal cancer. Results The study was firstly reported that IFI16 was overexpressed and positively correlated with caspase-1 in laryngeal carcinoma tissues. DHA alone or in combination with cisplatin significantly inhibited inflammasome activation and reduced IL-1β production in the xenograft tumor microenvironment of Hep-2 cell xenograft tumor in nude mice. Mechanistically, we found that DHA degraded RalB by inhibiting USP33 expression, leading to triggered autophagy. Meanwhile, enhanced autophagy can reduce the expression of RalB and USP33. Therefore, DHA depresses RalB, resulting in formation a positive feedback loop between USP33 and autophagy. Further, DHA promotes autophagy, which suppresses the IFI16/caspase-1 inflammasome activation and IL-1β production. Conclusions Therefore, our findings demonstrate that DHA may act as a RalB inhibitor to regulate the crosstalk between autophagy and IFI16/caspase-1 inflammasome, which inhibits IL-1β production in tumor microenvironment.

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Correlation Between the NLRP3 Inflammasome and the Prognosis of Patients With LSCC

Cited by 44 publications

References 27 publications

RalB degradation by dihydroartemisinin induces autophagy and IFI16/caspase-1 inflammasome depression in the human laryngeal squamous cell carcinoma

RalB degradation by dihydroartemisinin induces autophagy and IFI16/caspase-1 inflammasome depression in the human laryngeal squamous cell carcinoma

NLRP3 as Putative Marker of Ipilimumab-Induced Cardiotoxicity in the Presence of Hyperglycemia in Estrogen-Responsive and Triple-Negative Breast Cancer Cells

RalB degradation by dihydroartemisinin induces autophagy and IFI16/caspase-1 inflammasome depression in the human Laryngeal squamous cell carcinoma

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