Abstract
Resveratrol, a polyphenol abundant in peanuts, red wine and the skin of grapes, has been shown to have anti-cancer, anti-oxidant and anti-inflammatory activities, and may also have beneficial effects on allergic inflammation. We investigated the effects of resveratrol on human mast cell activation in comparison to the anti-allergy drug tranilast. In LAD2 mast cells, both resveratrol and tranilast inhibited degranulation induced by the mast cell activators substance P, IgE/anti-IgE, and compound 48/80. Resveratrol inhibition was immediate, preventing degranulation when added simultaneously to physiological stimuli, and the effect was sustained for up to 24 hrs. The inhibitory effect was not cAMP dependent, but may be attributable to calcium modulation, as resveratrol, and to a lesser extent tranilast, prevented substance P-induced increases in intracellular calcium. Resveratrol attenuated substance P-induced TNF and MCP-1 production and inhibited IgE-mediated release of cysteinyl leukotrienes, whereas tranilast was ineffective. Furthermore, both resveratrol and tranilast reduced expression of the high affinity IgE receptor, FceRI, on LAD2 cells. The effects of resveratrol on mast cell activation were more marked in human primary CD34+-derived mast cells (HuMC), and the polyphenol was significantly more efficacious than tranilast in these cells. In conclusion, resveratrol inhibited key aspects of human mast cell activation to physiological stimuli, and was comparable, if not more efficacious than the anti-allergy drug tranilast. Thus, resveratrol may be an effective therapeutic agent for the treatment of allergic disease.
Highlights
Resveratrol is an antimicrobial agent, produced by certain plants in response to pathogens [1,2]
Mast cells are the key mediators of allergic inflammation and anaphylactic responses, releasing histamine, proteases, arachidonic acid metabolites and proinflammatory cytokines and chemokines in response to numerous stimuli
These ubiquitous cells are distributed throughout vascularized tissue, at locales of pathogen entry, and can be activated by neuropeptides, such as substance P, complement proteins, bacterial, viral and parasitic components and antigen-crosslinking of IgE bound to its high affinity receptor FcεRI [8,9]
Summary
Resveratrol is an antimicrobial agent, produced by certain plants in response to pathogens [1,2]. The polyphenol is most abundant in peanuts, red wine and the skin of grapes This has lead to much research into potential health benefits of red wine, though the adequacy of resveratrol content for bioactivity is debatable. Due to its ability to inhibit arachidonic acid release and production of lipoxygenase and cyclooxygenase products [5,6,7], resveratrol may have beneficial effects on allergic inflammatory responses. Resveratrol reduces airway hyperresponsiveness, inflammation and allergen specific IgE levels in vivo in an OVA-induced mouse asthma model [10]. Preliminary in vitro animal studies report resveratrol-induced inhibition of degranulation and histamine release in mouse bone marrow mast cells (BMMC) [11], rat basophil-like cells (RBL-2H3) [12,13], and rat peritoneal mast cells [14], likely by suppressing tyrosine phosphorylation of ERK and PLC 1 [12]. Mouse BMMC cysteinyl leukotriene, prostaglandin D2, and TNF production are reduced by resveratrol [11]
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