Green and Roasted Coffee Extracts Inhibit Interferon-β Release in LPS-Stimulated Human Macrophages

Abstract

The anti-inflammatory activity of coffee extracts is widely recognized and supported by experimental evidence, in both in vitro and in vivo settings, mainly murine models. Here, we investigated the immunomodulatory properties of coffee extracts from green (GCE) and medium-roasted (RCE) Coffea canephora beans in human macrophages. The biological effect of GCE and RCE was characterized in LPS-stimulated THP-1-derived human macrophages (TDM) as a model of inflammation. Results showed decreased amounts of TNF-α, IL-6 and IL-1β and a strong dose-dependent inhibition of interferon-β (IFN-β) release. Molecular mechanism of IFN-β inhibition was further investigated by immunofluorescence confocal microscopy analysis that showed a diminished nuclear translocation of p-IRF-3, the main transcription factor responsible for IFN-β synthesis. The inhibition of IFN-β release by RCE and GCE was also confirmed in human primary CD14+ monocytes-derived macrophages (MDM). The main component of coffee extracts, 5-O-caffeoylquinic acid (5-CQA) also inhibited IFN-β production, through a mechanism occurring downstream to TLR4. Inhibition of IFN-β release by coffee extracts parallels with the activity of their main phytochemical component, 5-CQA, thus suggesting that this compound is the main responsible for the immunomodulatory effect observed. The application of 5-CQA and coffee derived-phytoextracts to target interferonopathies and inflammation-related diseases could open new pharmacological and nutritional perspectives.

A Global Picture of Molecular Changes Associated to LPS Treatment in THP-1 Derived Human Macrophages by Fourier Transform Infrared Microspectroscopy

“…THP-1 X-Blue™ monocytes were seeded in 100 mm cell culture dishes (Corning, Borre, France), 5 × 10 6 cells per dish in 10 mL of medium, and differentiated to TDM by exposure to 100 ng/mL of phorbol 12-myristate 13-acetate (PMA, InvivoGen, San Diego, CA, USA) for 3 days, as previously described [ 57 , 58 ]. Monocyte-to-macrophage differentiation was assessed by optical microscopy inspection.…”

The crucial regulatory role of type I interferon in inflammatory diseases

“…Studies have shown that after the combination of LPS and TLR 4, IRF 3 can be activated via phosphorylation of kinases TANK-binding kinase 1 (TBK1) and inhibitor of NF-κB (IκB) kinase (IKKε), inducing ISG to produce IFN-Is, modulating the process of inflammation [ 103 ]. In a separate study, Artusa et al reported that green coffee and roasted coffee extract can inhibit the effect of IRF 3, thereby inhibiting excessive IFN-β-induced inflammation [ 104 ]. Conversely, during viral infection, gastrodin (GTD) can promote the activation of IRF 3 in macrophages to facilitate the production of IFN-Is, resisting inflammation and anti-viral infection [ 105 ].…”

Microbiota-Derived Natural Products Targeting Cancer Stem Cells: Inside the Gut Pharma Factory

“…The health-promoting potential of plant extracts and plant-derived secondary metabolites is widely recognised [186][187][188]. Numerous beneficial effects of polyphenols on human health, such as antioxidant [189][190][191][192][193], anti-inflammatory [194][195][196], immunomodulatory [197][198][199], cardioprotective [200][201][202], neuroprotective [203][204][205], anti-carcinogenic [206][207][208], and prebiotic properties [209], have been reported. Thanks to the plethora of chemical structures they exhibit, natural anticancer compounds may act as cytotoxic agents [210][211][212], anti-mitotic agents [213], angiogenesis inhibitors [214,215], topoisomerase inhibitors [216], apoptosis inducers [217] and cancer invasion [218], migration [219] and proliferation inhibitors [220][221][222].…”