HBV inhibits LPS-induced NLRP3 inflammasome activation and IL-1β production via suppressing the NF-κB pathway and ROS production

Yu, Xin; Lan, Peixiang; Hou, Xuben; Han, Qiuju; Lü, Nan; Li, Tao; Jiao, Chenwei; Zhang, Jian; Zhang, Cai; Tian, Zhigang

doi:10.1016/j.jhep.2016.12.018

Cited by 248 publications

(185 citation statements)

References 44 publications

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“…Then, inflammasome activation stimulates the caspase-1-dependent processing of inflammatory molecules pro-IL-1β and pro-IL-18, resulting in the secretion of the mature form of these two cytokines [12]. Meantime, it has been well illustrated that ROS production is closely associated with the activation of NLRP3 inflammasome [13]. Furthermore, it has been reported that NLRP3 inflammasome plays an important role in maintaining intestinal homeostasis [11,14].…”

Section: Introductionmentioning

confidence: 99%

Short-Chain Fatty Acids Manifest Stimulative and Protective Effects on Intestinal Barrier Function Through the Inhibition of NLRP3 Inflammasome and Autophagy

Feng

Wang

et al. 2018

Cell Physiol Biochem

305

200

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Background/Aims: Short-chain fatty acids (SCFAs) are the major energy resources of intestinal epithelial cells. It has been reported that SCFAs can repair the dysfunction of intestinal barrier, however, the underlying mechanisms are still not fully understood. Here, we investigated the stimulative and protective effects of SCFAs on intestinal barrier function and the possible mechanisms. Methods: To investigate the effects of SCFAs on intestinal barrier function, the Caco-2 monolayers were exposed to acetate, propionate, butyrate respectively or simultaneously without or with lipopolysaccharide (LPS). Next, Caco-2 cells were treated with trichostatin A and etomoxir to identify whether SCFAs act as HDAC inhibitors or energy substances. To activate NLRP3 inflammasome and autophagy, Caco-2 cells were treated with LPS+ATP and rapamycin respectively without or with SCFAs. The transepithelial electrical resistance (TER) and paracellular permeability were respectively detected with a Millicell-ERS voltohmmeter and fluorescein isothiocyanate-labeled dextran. Immunoblotting and immunofluorescence were applied to analyze the expression and distribution of tight junction proteins, and the activation of NLRP3 inflammasome and autophagy. Results: Acetate (0.5mM), propionate(0.01mM) and butyrate (0.01mM) alone or in combination significantly increased TER, and stimulated the formation of tight junction. SCFAs also dramatically attenuated the LPS-induced TER reduction and paracellular permeability increase, accompanying significantly alleviated morphological disruption of ZO-1 and occludin. Meanwhile, the activation of NLRP3 inflammasome and autophagy induced by LPS were significantly inhibited by SCFAs. Trichostatin A imitated the inhibiting action of SCFAs on NLRP3 inflammasome, whereas etomoxir blocked the action of SCFAs on protecting intestinal barrier and inhibiting autophagy. In addition, the activation of autophagy and NLRP3 inflammasome by rapamycin and LPS+ATP resulted in TER reduction, paracellular permeability increase and morphological disruption of both ZO-1 and occludin, which was alleviated by SCFAs. Conclusion: It is suggested that SCFAs stimulate the formation of intestinal barrier, and protect the intestinal barrier from the disruption of LPS through inhibiting NLRP3 inflammasome and autophagy. In addition, SCFAs act as energy substances to protect intestinal barrier and inhibit autophagy, but act as HDAC inhibitors to suppress NLRP3 inflammasome. Furthermore, the mutual promoting action between NLRP3 inflammasome and autophagy would destroy intestinal barrier function, which could be alleviated by SCFAs.

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Section: Introductionmentioning

confidence: 99%

Short-Chain Fatty Acids Manifest Stimulative and Protective Effects on Intestinal Barrier Function Through the Inhibition of NLRP3 Inflammasome and Autophagy

Feng

Wang

et al. 2018

Cell Physiol Biochem

305

200

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“…Some studies reported that HBeAg inhibited AIM2 inflammasomes in peripheral blood mononuclear cells from patients infected with chronic hepatitis B (Chen, He, Chen, Zhang, & Wu, ). Moreover, HBeAg suppresses ROS production and LPS‐induced NLRP3 inflammasome activation (Yu et al, ). The interaction and mechanism between Etoposide, the topoisomerase II inhibitor, and caspase‐1 activation need further study in HepG2215 cells.…”

Section: Discussionmentioning

confidence: 99%

“…Inflammasome is a multiprotein complex, which senses danger signals, including different pathogen‐associated molecular patterns and damage‐associated molecular patterns and self‐cleaved caspase‐1, leading to pyroptosis and release of IL‐1β and IL‐18 (O'Neill, ; Vilaysane & Muruve, ). HBeAg, a viral protein, represses the activation of caspase‐1, the main effector caspase in pyroptosis and leads to the hepatitis B virus (HBV) persistence and immune tolerance (Yu et al, ). Absent in melanoma 2 (AIM2) (Chen et al, ; Ma et al, ) and IFN‐γ inducible protein 16 (IFI16; Lin et al, ; Yu et al, ), two members of the interferon‐inducible HIN‐200 protein family, are DNA sensors of inflammasome and recently recognized to play an important dual role in both innate immunity and HCC tumor pathology.…”

Section: Introductionmentioning

confidence: 99%

Dihydroartemisinin, an antimalarial drug, induces absent in melanoma 2 inflammasome activation and autophagy in human hepatocellular carcinoma HepG2215 cells

Shi

Wang

Ren

et al. 2019

Phytotherapy Research

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As an effective antimalarial drug, Dihydroartemisinin (DHA) is readily isolated from the traditional Chinese medicine of Artemisia annua. DHA is not only an autophagy promoter but also a substance with strong antitumor efficiency. The relationship between autophagy and inflammasomes has been suggested in hepatocellular carcinoma (HCC). However, there are few reports describing relationships between inflammasomes and autophagy in HCC therapy. The present study demonstrated that DHA suppressed cell proliferation in HepG2215 cells in a dose‐ and time‐dependent manner. The inhibitory activity is mediated by autophagy, in which reactive oxygen species (ROS) production induced nuclear and mitochondrial DNA damage. Then, DHA were first shown to promote AIM2/caspase‐1 inflammasome. Compared with the DHA group, the autophagy inhibitor 3‐MA significantly inhibited the expressions of activated Caspase‐1, a pyroptotic marker proteins. Meanwhile, repression of mTOR by rapamycin promoted autophagy and AIM2/caspase‐1 activation. The caspase‐1 inhibitor Z‐YVAD‐FMK also notably blocked autophagy cell death characterized by the downexpression of Beclin‐1 and LC3‐II. Additionally, the study demonstrated that DHA suppressed pseudopodium formation and cell mobility. Therefore, we first reveal a novel mechanism that DHA promotes AIM2/caspase‐1 inflammasome, which contributes to autophagy in HepG2215 cells. Moreover, nuclear and mitochondrial DNA damage was also involved in this process via ROS production.

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“…To confirm the significant roles of the inflammasomes in the induction of appropriate immune responses against HBV, some investigations reported that HBV uses some mechanisms to down-regulate their expression and alter their functions. For instance, Yu et al, reported that HBV, by HBeAg, uses some mechanisms to suppress IL-1β production via inhibition of NF-κB pathway and inhibits LPS/ROS-induced NLRP3 activation [40]. HBV also decreases expression of inflammasomes, especially AIM2, by reducing the mRNA stability of IFN regulatory factor 7 (IRF7), the main transcription factor for AIM2 gene [41].…”

Section: Inflammasomes Play Key Roles In the Eradication Of Viral Hepmentioning

confidence: 99%

Inflammasomes and their roles in the pathogenesis of viral hepatitis and their related complications: An updated systematic review

2019

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HBV inhibits LPS-induced NLRP3 inflammasome activation and IL-1β production via suppressing the NF-κB pathway and ROS production

Cited by 248 publications

References 44 publications

Short-Chain Fatty Acids Manifest Stimulative and Protective Effects on Intestinal Barrier Function Through the Inhibition of NLRP3 Inflammasome and Autophagy

Short-Chain Fatty Acids Manifest Stimulative and Protective Effects on Intestinal Barrier Function Through the Inhibition of NLRP3 Inflammasome and Autophagy

Dihydroartemisinin, an antimalarial drug, induces absent in melanoma 2 inflammasome activation and autophagy in human hepatocellular carcinoma HepG2215 cells

Inflammasomes and their roles in the pathogenesis of viral hepatitis and their related complications: An updated systematic review

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