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Xue R, Qiu J, Wei S, et al. Lycopene alleviates hepatic ischemia reperfusion injury via the Nrf2/HO-1 pathway mediated NLRP3 inflammasome inhibition in Kupffer cells. Ann Transl Med. 2021;9(8):631doi: 10.21037/atm-20-7084.
Xue, R., Qiu, J., Wei, S., Liu, M., Wang, Q., Wang, P., Sha, B., Wang, H., Shi, Y., Zhou, J., Rao, J., & Lu, L. (2021). Lycopene alleviates hepatic ischemia reperfusion injury via the Nrf2/HO-1 pathway mediated NLRP3 inflammasome inhibition in Kupffer cells. Annals of translational medicine, 9(8), 631. https://doi.org/10.21037/atm-20-7084
Xue, Rong, et al. "Lycopene alleviates hepatic ischemia reperfusion injury via the Nrf2/HO-1 pathway mediated NLRP3 inflammasome inhibition in Kupffer cells." Annals of translational medicine vol. 9,8 (2021): 631. doi: https://doi.org/10.21037/atm-20-7084
Xue R, Qiu J, Wei S, Liu M, Wang Q, Wang P, Sha B, Wang H, Shi Y, Zhou J, Rao J, Lu L. Lycopene alleviates hepatic ischemia reperfusion injury via the Nrf2/HO-1 pathway mediated NLRP3 inflammasome inhibition in Kupffer cells. Ann Transl Med. 2021 Apr;9(8):631. doi: 10.21037/atm-20-7084. PMID: 33987329; PMCID: PMC8106004.
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Ann Transl Med. 2021 Apr;9(8):631. doi: 10.21037/atm-20-7084.

Lycopene alleviates hepatic ischemia reperfusion injury via the Nrf2/HO-1 pathway mediated NLRP3 inflammasome inhibition in Kupffer cells.

Annals of translational medicine

Rong Xue, Jiannan Qiu, Song Wei, Mu Liu, Qi Wang, Peng Wang, Bowen Sha, Hao Wang, Yong Shi, Jinren Zhou, Jianhua Rao, Ling Lu

Affiliations

  1. School of Medicine, Southeast University, Nanjing, China.
  2. Hepatobiliary Center of The First Affiliated Hospital, Nanjing Medical University, Nanjing, China & Research Unit of Liver Transplantation and Transplant Immunology, Chinese Academy of Medical Sciences, Nanjing, China.
  3. The Affiliated Cancer Hospital (Jiangsu Cancer Hospital), Nanjing Medical University, Nanjing, China.
  4. State Key Laboratory of Reproductive Medicine, Nanjing Medical University, Nanjing, China.
  5. Jiangsu Collaborative Innovation Center of Biomedical Functional Materials, College of Chemistry and Materials Science, Nanjing Normal University, Nanjing, China.
  6. Jiangsu Key Lab of Cancer Biomarkers, Prevention and Treatment, Collaborative Innovation Center for Personalized Cancer Medicine, Nanjing Medical University, Nanjing, China.

PMID: 33987329 PMCID: PMC8106004 DOI: 10.21037/atm-20-7084

Abstract

BACKGROUND: Lycopene is a naturally occurring carotenoid found in many fruits and vegetables, which has antioxidant effects. Although lycopene's protective effect has been observed on ischemia reperfusion (IR) injury in different organs, the effect of lycopene on Kupffer cells (KCs) has not been clearly elucidated in IR-induced acute hepatic inflammatory injury.

METHODS: Mice were administered with either olive oil (10 mL/kg body weight) as the control or lycopene (20 mg/kg body weight) by gavage for 2 weeks before undergoing hepatic IR injury.

RESULTS: In this study, we observed that the levels of aspartate aminotransferases (AST), alanine aminotransferase (ALT), and the percentages of hepatocellular apoptosis in mice pretreated with lycopene were significantly lower than control mice. Lycopene inhibited F4/80+ macrophage and Ly6G+ neutrophil accumulation, which further decreased the levels of tumor necrosis factor-α (TNF-α), interleukin-1β (IL-1β), and interleukin 6 (IL-6). Interestingly, lycopene induced increased autophagy in KCs, which was evidenced by elevated autophagosomes and the increased protein level of LC3B. In these KCs, lycopene-induced upregulation of autophagy inhibited NOD-like receptor family pyrin domain-containing 3 protein (NLRP3) inflammasome activation, which was demonstrated by the reduced mRNA and protein levels of NLRP3, cleaved caspase-1, an apoptosis-associated speck-like protein containing a caspase recruitment domain (ASC), and IL-1β. Furthermore, 3-methyladenine, an autophagy inhibitor, abolished lycopene's inhibitory effect on the NLRP3 inflammasome in KCs, which led to increased hepatic IR injury. Intriguingly, we identified that the protein levels of nuclear factor erythroid 2-related factor 2 (Nrf2) and heme oxygenase 1 (HO-1) were elevated in KCs isolated from IR-stressed mice pretreated with lycopene. Nrf2-siRNA or HO-1-siRNA could block the autophagy activation enhanced by lycopene in KCs, resulting in the activation of the NLRP3 inflammasome and aggravated hepatic IR injury.

CONCLUSIONS: Our findings demonstrated that lycopene promoted Nrf2/HO-1 pathway activation and further suppressed the NLRP3 inflammasome via enhancing KC autophagy, which alleviated hepatic IR injury.

2021 Annals of Translational Medicine. All rights reserved.

Keywords: Kupffer cells (KCs); Lycopene; NLRP3 inflammasome; autophagy; hepatic ischemia reperfusion injury (hepatic IR injury)

Conflict of interest statement

Conflicts of Interest: All authors have completed the ICMJE uniform disclosure form (available at http://dx.doi.org/10.21037/atm-20-7084). LL serves as an unpaid Associate Editor-in-Chief of Annals of

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