Naringenin Ameliorates Acute Inflammation by Regulating Intracellular Cytokine Degradation

• Published in: The Journal of immunology (1950) Vol. 199; no. 10; pp. 3466 - 3477
• Main Authors: Jin, Lingtao, Zeng, Wenfeng, Zhang, Fayun, Zhang, Chunling, Liang, Wei
• Format: Journal Article
• Language: English
• Published: United States American Association of Immunologists 15.11.2017
• Subjects: Adaptive immunity; Animal models; Animals; Anti-Inflammatory Agents - therapeutic use; Bacteria; Basic Helix-Loop-Helix Leucine Zipper Transcription Factors - metabolism; Biodegradation; Cells, Cultured; Chemical and Drug Induced Liver Injury - drug therapy; Chemical and Drug Induced Liver Injury - immunology; Chemical compounds; Concanavalin A - immunology; Cytokines; Cytokines - metabolism; Disease Models, Animal; Endotoxemia; Endotoxemia - drug therapy; Endotoxemia - immunology; Female; Flavanones - therapeutic use; Hepatitis; Humans; Inflammation; Inflammation Mediators - metabolism; Interleukin 6; Intracellular; Lethality; Lipopolysaccharides; Lipopolysaccharides - immunology; Liver; Lymphocytes; Lymphocytes T; Lysosomes - metabolism; Macrophages; Mice; Mice, Inbred BALB C; Mice, Inbred C57BL; mRNA stability; Naringenin; Tumor necrosis factor-α; Viruses
• ISSN: 0022-1767; 1550-6606
• DOI: 10.4049/jimmunol.1602016

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 TLR signaling cascade, cytokine mRNA stability, 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.