concanavalin-a and naringenin

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.

Topics: Animals; Anti-Inflammatory Agents; Basic Helix-Loop-Helix Leucine Zipper Transcription Factors; Cells, Cultured; Chemical and Drug Induced Liver Injury; Concanavalin A; Cytokines; Disease Models, Animal; Endotoxemia; Female; Flavanones; Humans; Inflammation Mediators; Lipopolysaccharides; Lysosomes; Mice; Mice, Inbred BALB C; Mice, Inbred C57BL