Naringenin ameliorates acute inflammation by regulating intracellular cytokine degradation

Lingtao Jin, Wenfeng Zeng, Fayun Zhang, Chunling Zhang, Wei Liang

Research output: Contribution to journalArticlepeer-review

63 Scopus citations

Abstract

Ungoverned activation of innate and adaptive immunity results in acute inflammatory disease, such as bacteria-induced endotoxemia and fulminant hepatitis by virus infection. Thus, therapeutic control of inflammation is crucial for clinical management of many human diseases. In murine models of LPS-and Con A-induced liver injury, we found that naringenin, a natural predominant flavanone, is capable of protecting against lethality induced by LPS and preventing inflammation-induced organ injury. The protective effect of naringenin is mediated by reducing the levels of several inflammatory cytokines. Unexpectedly, naringenin inhibits TNF-α and IL-6 secretion in macrophages and T cells without interfering with the TLRsignaling cascade, cytokine mRNAstability, or protein translation. These results indicate the existence of a posttranslational control mechanism. Further studies show that naringenin enhances intracellular cytokine degradation through lysosome-and TFEB-dependent mechanisms. This study provides evidence that naringenin has the capacity to dampen cytokine production by regulating lysosome function. Thus, naringenin may represent a potential therapeutic agent for controlling inflammation-related diseases.

Original languageEnglish (US)
Pages (from-to)3466-3477
Number of pages12
JournalJournal of Immunology
Volume199
Issue number10
DOIs
StatePublished - Nov 15 2017
Externally publishedYes

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

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