Quercetin and Resveratrol Differentially Decrease Expression of the High-Affinity IgE Receptor (FcεRI) by Human and Mouse Mast Cells

Abstract

Mast cells (MC) synthesize and store proinflammatory mediators and are centrally important in atopic diseases such as asthma and atopic dermatitis. Quercetin a and resveratrol are plant derived polyphenolic compounds with anti-inflammatory properties that inhibit MC degranulation and mediator release. However, the underlying mechanism of these inhibitory effects on MC is poorly understood and it is unclear whether this is a general effect on all MC phenotypes. We have characterized and compared the effects of quercetin with resveratrol on human (LAD2) and mouse (MC/9 and BMMC) MC mediator release, receptor expression and FcεRI signaling to better understand the mechanisms involved in quercetin and resveratrol-mediated inhibition of MC activation. Quercetin significantly decreased the expression of FcεRI by BMMC and MC/9, although the effects on MC/9 were associated with a significant reduction in cell viability. Quercetin also inhibited antigen-stimulated TNF release by BMMC. Although neither quercetin nor resveratrol significantly altered antigen-stimulated BMMC degranulation or downstream signaling events such as phosphorylation of spleen tyrosine kinase (SYK) or extracellular signal-regulated kinase 1/2 (ERK), resveratrol inhibited ERK phosphorylation and FcεRI- stimulated degranulation in LAD2. Our data suggests that quercetin and resveratrol inhibit human and mouse MC differentially and that these effects are associated with modification of FcεRI expression, signaling (phosphorylation of SYK and ERK) and mediator release.

Agarose/crystalline nanocellulose (CNC) composites promote bone marrow-derived mast cell integrity, degranulation and receptor expression but inhibit production of de novo synthesized mediators

“…BMMC were cultured on the surface of the CNC/agarose matrix or on agarose alone for 18 h, and the size and granularity of the cell population was analyzed by flow cytometry ( Figures 3A, B ). Cells cultured on the agarose or CNC/agarose composites formed a normally distributed population of large and granular cells as measured by flow cytometry, similar to our previous studies ( Karamchand et al, 2021 ; Alam et al, 2022 ). To determine the effect of the CNC/agarose composites on cell viability, BMMC were washed with PBS and then exposed to propidium iodide, a DNA chelating dye that fluoresces when bound to DNA ( Benassi et al, 2022 ; Jin et al, 2022 ).…”

Resveratrol Protects against Skin Inflammation through Inhibition of Mast Cell, Sphingosine Kinase-1, Stat3 and NF-κB p65 Signaling Activation in Mice

“…This concentration of R is considered moderate and physiologically relevant for in vivo studies as well [ 69 ]. A recent study uncovered differences in the inhibitory effects of R in mouse bone marrow-derived MCs and the human Laboratory of Allergic Diseases (LAD)2 MC line [ 21 ]. Studies are currently ongoing in our lab aiming to compare the effects of R in mouse and human primary MCs.…”

“…We have previously reported inflammation-enabling functions of bioactive sphingolipid sphingosine-1-phosphate (S1P)-activated MCs in early-phase AD in mice, suggesting that controlling MC reactivity may prevent the development of AD [ 16 , 18 ]. It has been reported that R could inhibit MC inflammatory functions by reducing the expression of the high-affinity receptor for immunoglobulin (Ig)E, FcεRI , on human Laboratory of Allergic Diseases (LAD)2 MC line [ 21 ], preventing an increase in MC numbers in allergic enteritis, colitis [ 22 ], passive cutaneous anaphylaxis [ 23 ], and signal transducer and activator of transcription 3 (Stat3) activation [ 24 ]. Intriguingly, R was reported to not only stimulate S1P signaling [ 25 ] but also to inhibit S1P-producing sphingosine kinase 1 (SphK1) activity [ 26 ].…”

Resveratrol as a Promising Nutraceutical: Implications in Gut Microbiota Modulation, Inflammatory Disorders, and Colorectal Cancer

“…Resveratrol inhibits mast-cell activation, crucial in allergic responses, by blocking the MK2/3-PI3K/Akt axis, offering potential for various allergy disorders [ 100 ]. In human LAD-2 cells, resveratrol inhibits substance P, compound 48/80, and IgE-mediated degranulation, reducing pro-inflammatory cytokine release [ 101 ]. It also downregulates FcεRI (high-affinity IgE receptor) expression, further dampening allergic responses [ 101 ].…”

“…In human LAD-2 cells, resveratrol inhibits substance P, compound 48/80, and IgE-mediated degranulation, reducing pro-inflammatory cytokine release [ 101 ]. It also downregulates FcεRI (high-affinity IgE receptor) expression, further dampening allergic responses [ 101 ]. In humans, resveratrol may be effective in reducing allergic symptoms, particularly allergic rhinitis [ 102 ].…”