Differential anti-inflammatory pathway by xanthohumol in IFN-gamma and LPS-activated macrophages.
Macrophages are the main cells responsible for the innate immunity, and their activation by lipopolysaccharide (LPS) from Gram-negative bacteria or interferon (IFN)-gamma from host immune cells is important for controlling infections. However, the overwhelming activation of macrophages can cause a severe inflammatory state. This study investigated the inhibitory mechanism of xanthohumol (XN) against the inflammatory effectors (IL-1beta, TNF-alpha, and iNOS) in activated RAW264.7 macrophages by using different stimuli such as LPS, IFN-gamma, or LPS plus IFN-gamma. XN is a major prenylated chalcone found in hops, which is used to add bitterness and flavor to beer. XN reduced the expression of the LPS receptor components such as TLR4 and MD2 resulting in the suppression of NF-kappaB activation in LPS-activated RAW264.7 cells. In the IFN-gamma stimulated RAW264.7 cells, the binding activity of STAT-1alpha and IRF-1 was inhibited by XN. This suggests that differential signaling pathways are used by XN for the inhibition of excess inflammatory mediators depending on the stimuli in macrophages.
Cho
Young-Chang
YC
College of Pharmacy & Research Institute of Drug Development, Chonnam National University, Gwangju 500-757, Republic of Korea.
Kim
Hyun Jung
HJ
Kim
Young-Jun
YJ
Lee
Kwang Youl
KY
Choi
Hyun Jin
HJ
Lee
Ik-Soo
IS
Kang
Bok Yun
BY
D000818:Animals; D002460:Cell Line; D005419:Flavonoids; D050856:Interferon Regulatory Factor-1 / Q000378:metabolism; D007371:Interferon-gamma / Q000276:immunology; D053583:Interleukin-1beta / Q000378:metabolism; D008070:Lipopolysaccharides / Q000276:immunology; D051218:Lymphocyte Antigen 96 / Q000378:metabolism; D008262:Macrophage Activation; D008264:Macrophages / Q000187:drug effects* / Q000276:immunology* / Q000378:metabolism; D051379:Mice; D016328:NF-kappa B / Q000378:metabolism; D009569:Nitric Oxide / Q000378:metabolism; D052247:Nitric Oxide Synthase Type II / Q000378:metabolism*; D011427:Propiophenones / Q000494:pharmacology*; D050794:STAT1 Transcription Factor / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects; D051197:Toll-Like Receptor 4 / Q000378:metabolism; D014409:Tumor Necrosis Factor-alpha / Q000276:immunology / Q000378:metabolism
D005419:Flavonoids; D050856:Interferon Regulatory Factor-1; D053583:Interleukin-1beta; D008070:Lipopolysaccharides; C411728:Ly96 protein, mouse; D051218:Lymphocyte Antigen 96; D016328:NF-kappa B; D011427:Propiophenones; D050794:STAT1 Transcription Factor; D051197:Toll-Like Receptor 4; D014409:Tumor Necrosis Factor-alpha; D009569:Nitric Oxide; D007371:Interferon-gamma; D052247:Nitric Oxide Synthase Type II; C496317:Nos2 protein, mouse; C104536:xanthohumol