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Differential anti-inflammatory pathway by xanthohumol in IFN-gamma and LPS-activated macrophages
Young-Chang Cho1, Hyun Jung Kim, Young-Jun Kim
1College of Pharmacy & Research Institute of Drug Development, Chonnam National University, Gwangju 500-757, Republic of Korea.
Abstract:
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.
Insights
Xanthohumol (XN) inhibits excessive macrophage activation, a key part of innate immunity. It suppresses inflammatory mediators by targeting different pathways depending on the stimulus, like lipopolysaccharide (LPS) or interferon-gamma (IFN-gamma).
Area of Science:
- Immunology
- Pharmacology
- Biochemistry
Background:
- Macrophages are crucial for innate immunity, but overactivation causes severe inflammation.
- Lipopolysaccharide (LPS) and interferon-gamma (IFN-gamma) are key stimuli for macrophage activation.
- Xanthohumol (XN), a compound from hops, is investigated for its anti-inflammatory properties.
Purpose of the Study:
- To investigate the inhibitory mechanism of xanthohumol (XN) on inflammatory effectors in activated macrophages.
- To understand how XN affects inflammatory pathways triggered by LPS, IFN-gamma, or both.
Main Methods:
- RAW264.7 macrophage cell line was used.
- Cells were activated with LPS, IFN-gamma, or LPS plus IFN-gamma.
- The expression of inflammatory mediators (IL-1beta, TNF-alpha, iNOS) and signaling pathway components (TLR4, MD2, NF-kappaB, STAT-1alpha, IRF-1) was analyzed.
Main Results:
- XN reduced inflammatory mediators (IL-1beta, TNF-alpha, iNOS) in activated macrophages.
- In LPS-stimulated cells, XN suppressed TLR4 and MD2 expression, inhibiting NF-kappaB activation.
- In IFN-gamma-stimulated cells, XN inhibited the binding activity of STAT-1alpha and IRF-1.
Conclusions:
- Xanthohumol effectively inhibits macrophage-mediated inflammation.
- XN utilizes distinct signaling pathways to suppress inflammation based on the specific stimulus.
- XN shows potential as a therapeutic agent for inflammatory conditions.
