Mast Cell Regulation and Irritable Bowel Syndrome: Effects of Food Components with Potential Nutraceutical Use
Abstract
:1. Introduction
2. Mast Cells
3. Mast Cells and Irritable Bowel Syndrome
4. Nutraceuticals Affecting Mast Cell Activity
4.1. Lipids
4.1.1. Fatty Acids
4.1.2. Cannabinoids, Cannabinoid-Related Compounds and Other Lipidic Molecules
4.1.3. Fat-Soluble Vitamins
4.2. Amino Acids
4.3. Carotenoids
4.4. Polyphenolic Compounds
4.4.1. Flavonoids
4.4.2. Other Polyphenolic Compounds
4.5. Spices
4.5.1. Curcumin
4.5.2. Cinnamon Extract—Cinnamaldehyde
5. Conclusions
Author Contributions
Funding
Conflicts of Interest
Abbreviations
5-ASA | 5-aminosalicylic acid |
5-HT | serotonin |
AA | arachidonic acid |
ALA | α-linolenic acid |
Akt | protein kinase B |
APC | adenomatous polyposis coli |
BMMCs | bone marrow-derived mast cells |
C2 | canine mastocytoma cell line |
CCL | C-C motif chemokine ligand |
CD | Crohn’s disease |
CNS | central nervous system |
COX | cyclooxygenase |
CRF | corticotropin releasing factor |
CXCL | Chemokine (C-X-C motif) ligand |
CXCR2 | chemokine (C-X-C motif) ligand 2 (Interleukin 8 receptor beta) |
DHA | docosahexaenoic acid |
DNFB | dinitrofluorobenzene |
DRG | dorsal root ganglia |
DSCG | disodium cromoglicate |
EGCG | epigallocatechin-3-gallate |
ENS | enteric nervous system |
EPA | eicosapentaenoic acid |
ERK | extracellular signal-regulated kinase |
ET-1 | endothelin 1 |
FcεRI | high-affinity IgE receptor |
FGF | fibroblast growth factor |
FODMAPs | fermentable oligosaccharides, disaccharides, monosaccharides and polyols |
GATA-1 | GATA binding protein-1 |
GATA-2 | GATA binding protein-2 |
GI | gastrointestinal |
GLA | γ-linolenic acid |
GM-CSF | granulocyte macrophage colony-stimulating factor |
IBD | inflammatory bowel disease |
IBS | irritable bowel syndrome |
IBS-C | IBS with predominant constipation |
IBS-D | IBS with predominant diarrhea |
IBS-M | mixed IBS |
IBS-U | unclassified IBS |
IFN | interferon |
Ig | immunoglobulin |
IL | interleukin |
IP3 | inositol-1,4,5-triphosphate |
JAM | junctional adhesion molecule |
JNK | c-Jun NH2–terminal kinase |
LIF | leukemia inhibitory factor |
LPS | lipopolysaccharide |
LT | leukotriene |
MAPK | mitogen-activated protein kinase |
MBP | eosinophil major basic protein |
MC-CPA | carboxypeptidase A3 |
MCP | monocyte chemotactic protein |
MIP | macrophage inflammatory protein |
MMP | matrix metalloproteinase |
MMP9 | matrix metallopeptidase 9 |
MRGPRX2 | MAS-related G-protein-coupled receptor X2 |
MS | maternal separation test |
MyD88 | myeloid differentiation primary response 88 |
NFκβ | nuclear factor κβ |
NGF | nerve growth factor |
NK | natural killer |
NO | nitric oxide |
PAF | platelet activating factor |
PAMP | pathogen-associated molecular pattern |
PDGF | platelet-derived growth factor |
PG | prostaglandin |
PI-IBS | post-infectious IBS |
PI3K-Akt | phosphoinositide 3-OH kinase-protein kinase B |
PKC | protein kinase C |
PKC θ | calcium-insensitive protein kinase C theta |
PLCγ1 | phosphoinositide-specific phospholipase C |
pp125 (FAK) | focal adhesion kinase |
PPARγ | peroxisome proliferator-activated receptor γ |
PUFA | polyunsaturated fatty acid |
RANTES | regulated upon activation, normal T cell expressed and secreted |
RBL | Rat basophilic leukemia |
RBL-2H3 | rat basophilic leukemia mast cell line |
ROS | reactive oxygen species |
S1P1 | sphingosine-1-phosphate (S1P) receptor 1 |
S1P2 | sphingosine-1-phosphate (S1P) receptor 2 |
SCF | stem cell factor |
SCFA | short chain fatty acid |
SOC | store-operated Ca2+ channels |
SP | substance P |
SphK | sphingosine kinase |
SyK | tyrosine-protein kinase SYK or spleen tyrosine kinase |
TGF | transforming growth factor |
TLR | toll-like receptors |
TNF | tumor necrosis factor |
Treg | regulatory T cells |
VCAM-1 | vascular cell adhesion molecule 1 |
VEGF | vascular endothelial growth factor |
VIP | vasoactive intestinal peptide |
VDR | vitamin D receptor |
WRS | wrap restraint stress |
References
- Black, C.J.; Ford, A.C. Global burden of irritable bowel syndrome: Trends, predictions and risk factors. Nat. Rev. Gastro. Hepat. 2020, 17, 473–486. [Google Scholar] [CrossRef] [PubMed]
- Grad, S.; Dumitrascu, D.L. Irritable Bowel Syndrome Subtypes: New Names for Old Medical Conditions. Dig. Dis. 2020, 38, 122–127. [Google Scholar] [CrossRef] [PubMed]
- Creed, F. Review article: The incidence and risk factors for irritable bowel syndrome in population-based studies. Aliment Pharm. Therap. 2019, 50, 507–516. [Google Scholar] [CrossRef] [PubMed]
- Canavan, C.; West, J.; Card, T. Review article: The economic impact of the irritable bowel syndrome. Aliment Pharm. Therap. 2014, 40, 1023–1034. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Spiller, R.; Major, G. IBS and IBD-separate entities or on a spectrum? Nat. Rev. Gastro. Hepat. 2016, 13, 613–621. [Google Scholar] [CrossRef] [PubMed]
- Balmus, I.M.; Ciobica, A.; Cojocariu, R.; Luca, A.C.; Gorgan, L. Irritable Bowel Syndrome and Neurological Deficiencies: Is There A Relationship? The Possible Relevance of the Oxidative Stress Status. Medicina 2020, 56, 175. [Google Scholar] [CrossRef] [Green Version]
- Ng, Q.X.; Soh, A.Y.S.; Loke, W.; Lim, D.Y.; Yeo, W.S. The role of inflammation in irritable bowel syndrome (IBS). J. Inflamm. Res. 2018, 11, 345–349. [Google Scholar] [CrossRef] [Green Version]
- Verne, G.N.; Price, D.D. Irritable bowel syndrome as a common precipitant of central sensitization. Curr. Rheumatol. Rep. 2002, 4, 322–328. [Google Scholar] [CrossRef]
- Casado-Bedmar, M.; Keita, Å.V. Potential neuro-immune therapeutic targets in irritable bowel syndrome. Therap. Adv. Gastroenter. 2020, 13, 1756284820910630. [Google Scholar] [CrossRef]
- Labanski, A.; Langhorst, J.; Engler, H.; Elsenbruch, S. Stress and the brain-gut axis in functional and chronic-inflammatory gastrointestinal diseases: A transdisciplinary challenge. Psychoneuroendocrinology 2020, 111, 104501. [Google Scholar] [CrossRef]
- Thangam, E.B.; Jemima, E.A.; Singh, H.; Baig, M.S.; Khan, M.; Mathias, C.B.; Church, M.K.; Saluja, R. The Role of Histamine and Histamine Receptors in Mast Cell-Mediated Allergy and Inflammation: The Hunt for New Therapeutic Targets. Front Immunol. 2018, 9, 1873. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- da Silva, E.Z.; Jamur, M.C.; Oliver, C. Mast Cell Function: A New Vision of an Old Cell. Journal of Histochem. Cytochem 2014, 62, 698–738. [Google Scholar] [CrossRef] [PubMed]
- Galli, S.J.; Borregaard, N.; Wynn, T.A. Phenotypic and functional plasticity of cells of innate immunity: Macrophages, mast cells and neutrophils. Nat. Immunol. 2011, 12, 1035–1044. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Gentek, R.; Ghigo, C.; Hoeffel, G.; Bulle, M.J.; Msallam, R.; Gautier, G.; Launay, P.; Chen, J.; Ginhoux, F.; Bajénoff, M. Hemogenic Endothelial Fate Map** Reveals Dual Developmental Origin of Mast Cells. Immunity 2018, 48, 1160–1171. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Li, Z.; Liu, S.; Xu, J.; Zhang, X.; Han, D.; Liu, J.; **, K.; Savelkoul, P.; Harthoorn, L.; Jahnsen, F.; Garssen, J.; et al. Oral exposure to the free amino acid glycine inhibits the acute allergic response in a model of cow’s milk allergy in mice. Nut. Res. 2018, 58, 95–105. [Google Scholar] [CrossRef]
- Sakai, S.; Sugawara, T.; Matsubara, K.; Hirata, T. Inhibitory effect of carotenoids on the degranulation of mast cells via suppression of antigen-induced aggregation of high affinity IgE receptors. J. Biol. Chem. 2009, 284, 28172–28179. [Google Scholar] [CrossRef] [Green Version]
- Kim, H.; Ahn, Y.; Lee, G.; Cho, S.; Kim, J.; Lee, C.; Lim, B.; Ju, S.; An, W. Effects of astaxanthin on dinitrofluorobenzene-induced contact dermatitis in mice. Mol. Med. Rep. 2015, 12, 3632–3638. [Google Scholar] [CrossRef] [Green Version]
- Sato, Y.; Akiyama, H.; Suganuma, H.; Watanabe, T.; Nagaoka, M.H.; Inakuma, T.; Goda, Y.; Maitani, T. The feeding of -carotene down-regulates serum IgE levels and inhibits the type I allergic response in mice. Biol. Pharm. Bull. 2004, 27, 978–984. [Google Scholar] [CrossRef] [Green Version]
- Kinoshita, T.; Koike, K.; Mwamtemi, H.H.; Ito, S.; Ishida, S.; Nakazawa, Y.; Kurokawa, Y.; Sakashita, K.; Higuchi, T.; Takeuchi, K.; et al. Retinoic acid is a negative regulator for the differentiation of cord blood-derived human mast cell progenitors. Blood 2000, 95, 2821–2828. [Google Scholar] [CrossRef] [PubMed]
- Hjertson, M.; Kivinen, P.; Dimberg, L.; Nilsson, K.; Harvima, I.; Nilsson, G. Retinoic acid inhibits in vitro development of mast cells but has no marked effect on mature human skin tryptase- and chymase-positive mast cells. J. Investig. Dermatol. 2003, 120, 239–245. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Ishida, S.; Kinoshita, T.; Sugawara, N.; Yamashita, T.; Koike, K. Serum inhibitors for human mast cell growth: Possible role of retinol. Eur. J. Allergy. Clin. Immunol. 2003, 58, 1044–1052. [Google Scholar] [CrossRef] [PubMed]
- Astorquiza, M.I.; Helle, B.; Vergara, R.E. Effect of vitamin A onthe in vitro degranulation of mouse mastcells. Allergol. Immunopathol. 1980, 8, 87–90. [Google Scholar]
- Middleton, E., Jr.; Drzewiecki, G. Flavonoid inhibition of human basophil histamine release stimulated by various agents. Biochem. Pharmacol. 1984, 33, 3333–3338. [Google Scholar] [CrossRef]
- Trnovsky, J.; Letourneau, R.; Haggag, E.; Boucher, W.; Theoharides, T.C. Quercetin-induced expression of rat mast cell protease II and accumulation of secretory granules in rat basophilic leukemia cells. Biochem. Pharmacol. 1993, 46, 2315–2326. [Google Scholar] [CrossRef]
- Alexandrakis, M.; Singh, L.; Boucher, W.; Letourneau, R.; Theofilopoulos, P.; Theoharides, T.C. Differential effect of flavonoids on inhibition of secretion and accumulation of secretory granules in rat basophilic leukemia cells. Int. J. Immunopharmacol. 1999, 21, 379–390. [Google Scholar] [CrossRef]
- Kimata, M.; Inagaki, N.; Nagai, H. Effects of luteolin and other flavonoids on IgE-mediated allergic reactions. Planta. Med. 2000, 66, 25–29. [Google Scholar] [CrossRef]
- Kimata, M.; Shichijo, S.; Miura, T.; Serizawa, I.; Inagaki, N.; Nagai, H. Effects of luteolin, quercetin and baicalein on immunoglobulin E-mediated mediator release from human cultured mast cells. Clin. Exp. Allergy 2000, 30, 501–508. [Google Scholar] [CrossRef]
- Seelinger, G.; Merfort, I.; Schempp, C.M. Anti-oxidant, anti-inflammatory and anti-allergic activities of luteolin. Planta. Med. 2008, 74, 1667–1677. [Google Scholar] [CrossRef]
- Park, H.H.; Lee, S.; Son, K.Y.; Park, S.B.; Kim, M.S.; Choi, E.J.; Singh, T.S.; Ha, J.H.; Lee, M.G.; Kim, J.E.; et al. Flavonoids inhibit histamine release and expression of proinflammatory cytokines in mast cells. Arch. Pharm. Res. 2008, 31, 1303–1311. [Google Scholar] [CrossRef] [PubMed]
- Kempuraj, D.; Madhappan, B.; Chrístodoulou, S.; Boucher, W.; Cao, J.; Papadopoulou, N.; Cetrulo, C.L.; Theoharides, T.C. Flavonols inhibit proinflammatory mediator release, intracellular calcium ion levels and protein kinase C phosphorylation in human mast cells. Br. J. Pharmacol. 2005, 145, 934–944. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Yang, Y.; Oh, J.M.; Heo, P.; Shin, J.Y.; Kong, B.; Shin, J.; Lee, J.C.; Oh, J.S.; Park, K.W.; Lee, C.H.; et al. Polyphenols differentially inhibit degranulation of distinct subsets of vesicles in mast cells by specific interaction with granule-type-dependent SNARE complexes. Biochem. J. 2013, 450, 537–546. [Google Scholar] [CrossRef] [PubMed]
- Hagenlocher, Y.; Feilhauer, K.; Schäffer, M.; Bischoff, S.C.; Lorentz, A. Citrus peel polymethoxyflavones nobiletin and tangeretin suppress LPS- and IgE-mediated activation of human intestinal mast cells. Eur. J. Nutr. 2017, 56, 1609–1620. [Google Scholar] [CrossRef]
- Tanaka, T.; Iuchi, A.; Harada, H.; Hashimoto, S. Potential Beneficial Effects of Wine Flavonoids on Allergic Diseases. Diseases 2019, 7, 8. [Google Scholar] [CrossRef] [Green Version]
- Hagenlocher, Y.; Gommeringer, S.; Held, A.; Feilhauer, K.; Köninger, J.; Bischoff, S.C.; Lorentz, A. Nobiletin acts anti-inflammatory on murine IL-10-/- colitis and human intestinal fibroblasts. Eur. J. Nutr. 2019, 58, 1391–1401. [Google Scholar] [CrossRef]
- Hubert, J.; Berger, M.; Nepveu, F.; Paul, F.; Daydé, J. Effects of fermentation on the phytochemical composition and antioxidant properties of soy germ. Food Chem. 2008, 109, 709–721. [Google Scholar] [CrossRef]
- Moussa, L.; Bézirard, V.; Salvador-Cartier, C.; Bacquié, V.; Houdeau, E.; Théodorou, V. A new soy germ fermented ingredient displays estrogenic and protease inhibitor activities able to prevent irritable bowel syndrome-like symptoms in stressed female rats. Clin. Nutr. 2013, 32, 51–58. [Google Scholar] [CrossRef]
- Inoue, T.; Suzuki, Y.; Ra, C. Epigallocatechin-3-gallate inhibits mast cell degranulation, leukotriene C4 secretion, and calcium influx via mitochondrial calcium dysfunction. Free Radic. Biol. Med. 2010, 49, 632–640. [Google Scholar] [CrossRef]
- Inoue, T.; Suzuki, Y.; Ra, C. Epigallocatechin-3-gallate induces cytokine production in mast cells by stimulating an extracellular superoxide-mediated calcium influx. Biochem. Pharmacol. 2011, 82, 1930–1939. [Google Scholar] [CrossRef]
- Khan, N.; Mukhtar, H. Tea Polyphenols in promotion of human health. Nutrients 2018, 11, 39. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Matsuo, N.; Yamada, K.; Shoji, K.; Mori, M.; Sugano, M. Effect of tea polyphenols on histamine release from rat basophilic leukemia (RBL-2H3) cells: The structure-inhibitory activity relationship. Allergy 1997, 52, 58–64. [Google Scholar] [CrossRef] [PubMed]
- Yamashita, K.; Suzuki, Y.; Matsui, T.; Yoshimaru, T.; Yamaki, M.; Suzuki-Karasaki, M.; Hayakawa, S.; Shimizu, K. Epigallocatechin gallate inhibits histamine release from rat basophilic leukemia (RBL-2H3) cells: Role of tyrosine phosphorylation. Biochem. Biophys. Res. Commun. 2000, 274, 603–608. [Google Scholar] [CrossRef] [PubMed]
- Murata, K.; Takano, S.; Masuda, M.; Iinuma, M.; Matsuda, H. Anti-degranulating activity in rat basophilic leukemia RBL-2H3 cells of flavanone glycosides and their aglycones in citrus fruits. J. Nat. Med. 2013, 67, 643–646. [Google Scholar] [CrossRef]
- Fiorani, M.; Accorsi, A.; Blasa, M.; Diamantini, G.; Piatti, E. Flavonoids from Italian multi-floral honeys reduce the extracellular ferricyanide in human red blood cells. J. Agric. Food Chem. 2006, 54, 8328–8334. [Google Scholar] [CrossRef]
- Guendouz, M.; Haddi, A.; Grar, H.; Kheroua, O.; Saidi, D.; Kaddouri, H. Preventive effects of royal jelly against anaphylactic response in a murine model of cow’s milk allergy. Pharm. Biol. 2017, 55, 2145–2152. [Google Scholar] [CrossRef] [Green Version]
- Gupta, S.C.; Kismali, G.; Aggarwal, B.B. Curcumin, a component of turmeric: From farm to pharmacy. Biofactors 2013, 39, 2–13. [Google Scholar] [CrossRef]
- Lee, J.H.; Kim, J.W.; Ko, N.Y.; Mun, S.H.; Her, E.; Kim, B.K.; Han, J.W.; Lee, H.Y.; Beaven, M.A.; Kim, Y.M.; et al. Curcumin, a constituent of curry, suppresses IgE-mediated allergic response and mast cell activation at the level of Syk. J. Allergy Clin. Immunol. 2008, 121, 1225–1231. [Google Scholar] [CrossRef]
- Hanai, H.; Iida, T.; Takeuchi, K.; Watanabe, F.; Maruyama, Y.; Andoh, A.; Tsujikawa, T.; Fujiyama, Y.; Mitsuyama, K.; Sata, M.; et al. Curcumin maintenance therapy for ulcerative colitis: Randomized, multicenter, double-blind, placebo-controlled trial. Clin. Gastroen. Hepatol. 2006, 4, 1502–1506. [Google Scholar] [CrossRef]
- Lang, A.; Salomon, N.; Wu, J.C.; Kopylov, U.; Lahat, A.; Har-Noy, O.; Ching, J.Y.; Cheong, P.K.; Avidan, B.; Gamus, D.; et al. Curcumin in combination with mesalamine induces remission in patients with mild-to-moderate ulcerative colitis in a randomized controlled trial. Clin. Gastroen. Hepatol. 2015, 13, 1444–1449. [Google Scholar] [CrossRef]
- Bundy, R.; Walker, A.F.; Middleton, R.W.; Booth, J. Turmeric extract may improve irritable bowel syndrome symptomology in otherwise healthy adults: A pilot study. J. Altern. Complement. Med. 2004, 10, 1015–1018. [Google Scholar] [CrossRef] [PubMed]
- Portincasa, P.; Bonfrate, L.; Scribano, M.L.; Kohn, A.; Caporaso, N.; Festi, D.; Campanale, M.C.; Di Rienzo, T.; Guarino, M.; Taddia, M.; et al. Curcumin and Fennel Essential Oil Improve Symptoms and Quality of Life in Patients with Irritable Bowel Syndrome. J. Gastrointestin. Liver. Dis. 2016, 25, 151–157. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Hagenlocher, Y.; Bergheim, I.; Zacheja, S.; Schäffer, M.; Bischoff, S.C.; Lorentz, A. Cinnamon extract inhibits degranulation and de novo synthesis of inflammatory mediators in mast cells. Allergy 2013, 68, 490–497. [Google Scholar] [CrossRef] [PubMed]
- Hagenlocher, Y.; Hösel, A.; Bischoff, S.; Lorentz, A. Cinnamon extract reduces symptoms, inflammatory mediators and mast cell markers in murine IL-10−/− colitis. J. Nut. Biochem. 2016, 30, 85–92. [Google Scholar] [CrossRef]
- Hagenlocher, Y.; Kiessling, K.; Schäffer, M.; Bischoff, S.C.; Lorentz, A. Cinnamaldehyde is the main mediator of cinnamon extract in mast cell inhibition. Eur. J. Nutr. 2015, 54, 1297–1309. [Google Scholar] [CrossRef]
Category | Specific Molecules |
---|---|
Biogenic amines | Histamine, 5-HT, Dopamine, Polyamines |
Lysosomal Enzymes | β-hexosaminidase, β-glucuronidase, β-d-galactosidase, Arylsulphatase A, Cathepsins |
Proteases | Chymase, Tryptase, Carboxypeptidase A, Granzyme B, MMPs, Renin |
Other Enzymes | Kinogenases, Heparanase, Angiogenin, Caspase-3, COX 1 and 2 |
Proteoglycans/Glycosaminoglycans | Serglycin, Heparin |
Cytokines | TNF, IL-1, IL-2, IL-3, IL-4, IL-5, IL-6, IL-8, IL-9, IL-10, IL-11, IL-12, IL-13IL-15, IL-16 IL-17, IL-18, IL-25, IL-33, IFN, MIP-1α and 2β |
Chemokines | RANTES (CCL5), eotaxin (CCL11), MCP-1 (CCL2), MCP-3 (CCL7), MCP-4 |
Growth Factors | TGF-β, VEGF, NGF, SCF, GM-CSF, FGF, NGF, PDGF, LIF |
Peptides | CRF, Endorphin, ET-1, Cathelicidin (LL37), Defensins, SP, VIP |
Phospolipid Metabolites | PGD2, PGE2, LTB4, LTC4, PAF |
Reactive Oxygen Species | NO |
Others | MBP, Complement Factors C3 and C5 |
Compound | System | Effect a | Mechanism of Action | Reference |
---|---|---|---|---|
In Vitro Studies | ||||
AA (20:4n-6) | LAD2 HMC-1 | ↑ PGD2 ↑ TNF-α | ROS generation and MAPK signaling | [126] |
AA (20:4n-6) | C2 | ↑ Tryptase activity ↑ PGE2 production ↑ Histamine release | Changes in cellular redox state and lipid peroxidation (suggested) | [132] |
ALA (18:3n-3) | MC/9, BMMCs | ↓ IL-4, IL-5 and IL-13 production | Modulation of nuclear expression of GATA-1 and GATA-2 | [127] |
ALA (18:3n-3) | C2 | ↓ Tryptase activity ↓ PGE2 production ↓ Histamine release | [130,131] | |
DHA (226n-3) | LAD2 HMC-1 | ↓ Il-4 ↓ IL-13 ↓ ROS generation | MAPK signaling | [126] |
DHA (22:6n-3) | HMC-1 | ↓ TNF-α release | PPARγ-dependent activation | [129] |
EPA (20:5n-3) | LAD2 HMC-1 | ↓ Il-4 ↓ IL-13 ↓ ROS generation | MAPK signaling | [126] |
EPA (20:5n-3) | Mast cells cultured from human umbilical cord mononuclear cells | ↓ PGD2 generation | Inhibition of COX-1 and COX-2 activities | [128] |
EPA (20:5n-3) | MC/9, BMMCs | ↓ IL-4, Il-5 and IL-13 production | Modulation of nuclear expression of GATA-1 and GATA-2 | [127] |
EPA (20:5n-3) | HMC-1 | ↓ TNF-α release | PPARγ-dependent activation | [129] |
EPA (20:5n-3) | MC/9, BMMCs | ↓ IL-4, Il-5 and IL-13 production | Modulation of nuclear expression of GATA-1 and GATA-2 | [127] |
EPA (20:5n-3) | C2 | ↑ PGE2 production ↑ Histamine release | Changes in cellular redox state and lipid peroxidation (suggested) | [132] |
GLA (18:3n-6) | C2 | ↑ Tryptase activity ↑ Histamine release | [130,131] | |
In Vivo Studies | ||||
Diet rich in n-6 linoleic acid, saturated fatty acids (safflower oil) | Intestinal mast cell-IgE-mediated inflammatory reaction model in rats | ↓ Rat chymase II | [133] | |
Fish oil containing high level of omega-3 fatty acids | NC/Nga murine atopic model. | ↓ Severity of dermatitis ↓ Thickening of epidermis/dermis | [127] | |
Sodium butyrate (SCFA) | Pig | ↓ Histamine content ↓ Tryptase content/expression ↓ TNF-α content/expression ↓ IL-6 content/expression | JNK signaling pathways | [136] |
Compound | System | Effect a | Mechanism of Action | Reference |
---|---|---|---|---|
Cannabinoids and Cannabinoid-Related Compounds | ||||
Cannabidiol | LPS-induced intestinal inflammation in mice | ↓ Chymase up-regulation ↓ MMP9 up-regulation | Involvement of astroglial signaling neurotrophin S100B and PPARγ-dependent mechanisms | [138] |
Palmithoylethanolamide | Canine skin mast cells | ↓ Histamine release ↓ PGD2 release ↓ TNF-α release | [140] | |
Palmithoylethanolamide | HMC-1 | ↓ NGF release | GPR55-mediated | [141] |
Palmithoylethanolamide | Neuropathic pain (chronic constriction injury of sciatic nerve in mice) | ↓ TNF-α release ↓ NGF release | [146] | |
Palmithoylethanolamide | Spinal cord injury (mice) | ↓ Proteases (tryptase and chymase) release | [147] | |
Palmithoylethanolamide/Polydatin | Clinical trial in IBS patients (NCT01370720) | Without changes in mast cell counts | [149] | |
Other Lipidic Molecules | ||||
Ceramide/sphingosine | Mouse BMMCs | ↓ IL-5, IL-10 and IL-13 production | Inhibition of PI3K-Akt pathway | [151] |
Sphingosine-1-phosphate | Mouse BMMCs RBL-2H3 cells (rat) | ↑ LT synthesis ↑ TNF-production ↑ Chemokines production ↑ β-hexosaminidase release | FcεRI-mediated activation of SphK-S1P1/S1P2 pathway | [150,152] |
Compound | System | Effect a | Mechanism of Action | Reference |
---|---|---|---|---|
Vitamin D3 (calcitriol) | HMC-1 cells (human) RBL-2H3 cells (rat) p815 cells (mouse) Mouse BMMCs | ↓ TNF-α expression ↓ TNF-α production ↓ Histamine release | Inhibition of FcεRI and MyD88, associated to decreased Syk phosphorylation and MAPK and NFκB levels. VDR binding to the TNF-α promoter leading to decreased acetylation of histone H3/H4, RNA polymerase II and OCT1 (a transcription factor of TNF-α) at the promoter locus, repressing TNF-α expression | [153] |
Vitamin D3 (calcitriol) | Ovalbumin –sensitized mice with vitamin D-supplemented diet | ↓ Serum TNF-α ↓ Serum histamine | [153] | |
Vitamin E (tocopherols) | C2 (canine) | ↓ Histamine release ↓ PGD2 release ↓ Chymase activity | [155] | |
Vitamin E (tocopherols) | Rat peritoneal mast cells | ↓ Histamine release | Changes in lipid peroxidation through the lipoxygenase pathway | [156] |
Compound | System | Effect a | Mechanism of Action | Reference |
---|---|---|---|---|
Arginine + Glutamine | Human intestinal mast cells | ↓ LT C4 secretion ↓ CCL2 expression ↓ CCL4 expression ↓ IL-8 expression | Decreased activation levels of signaling molecules of the MAPK family (extracellular signal-regulated kinase, JNK and p38) and the Akt | [158] |
Glycine | Murine model of allergy to cow’s milk | ↓ Plasma levels of mouse mast cell protease-1 | [160] |
Compound | System | Effect a | Mechanism of Action | Reference |
---|---|---|---|---|
Carotenoids (fucoxanthin, astaxanthin, zeaxanthin and β-carotene) | Rat RBL-2H3 cells Mouse BMMCs | ↓ β-hexosaminidase release | Inhibition of FcεRI-mediated intracellular signaling: phosphorylation of Lyn kinase and Fyn kinase | [161] |
α- and β-carotene | Ovalbumin–sensitized mice | ↓ Histamine release | [163] | |
Astaxanthin | DNFB-induced contact dermatitis in mice | ↓TNF-α levels ↓ IFN-γ levels | [162] | |
Astaxanthin | Rat RBL-2H3 cells | ↓ Histamine release ↓ β-hexosaminidase | [162] |
Compound | System | Effect a | Mechanism of Action | Reference |
---|---|---|---|---|
Quercitin | RBL-2H3 cells | ↑ Rat mast cell protease II synthesis ↑ Accumulation of secretory granules ↓ Histamine release ↓ β-hexosaminidase release | [168,170] | |
Flavone | RBL-2H3 cells | ↑ Accumulation of secretory granules ↓ β-hexosaminidase release | [168] | |
Kaempferol | RBL-2H3 cells | ↓ β-hexosaminidase release | [168] | |
Myricetin | RBL-2H3 cells | ↓ β-hexosaminidase release | [168] | |
Luteolin, baicalein, quercetin | BMMCs Rat peritoneal mast cells | ↓ Histamine release ↓ Il-6 production ↓ TNF-α production | [171] | |
Luteolin, baicalein, quercetin | Human cultured mast cells | ↓ Histamine release ↓ LTs release ↓ PGD2 release | Inhibition of Ca2+ influx and PKC, ERKs and JNK signaling pathways | [172] |
Kaempferol, myrecitin, quercetin, rutin, fisetin | RBL-2H3 cells HMC-1 cells | ↓ Histamine release ↓ TNF-α expression and release ↓ IL-1β expression and release ↓ IL-6 expression and release ↓ Il-8 expression and release | Suppression of NFκB activation (fisetin, myricetin and rutin) | [174] |
Quercetin, kaempferol, 14yricetin, morin | Human umbilical cord BMMCs | ↓ Histamine release ↓ TNF-α release ↓ IL-6 release ↓ IL-8 release | Suppression of intracellular Ca2+, inhibition of PKC θ phosphorylation | [175] |
Nobiletin, tangeretin | Human intestinal mast cells | ↓ CXCL8 expression ↓ CCL3 expression ↓ CCL4 expression ↓ IL-1β expression (tangeretin) ↓ TNF-α expression ↓ β–hexosaminidase release (nobiletin) ↓ cysteinyl LTC4 (nobiletin) | Reduced phosphorylation of ERK1/2 | [177] |
Nobiletin | Murine IL-10 knockout model of colitis | ↓ Mast cell density (colon) ↓ Mast cell degranulation (colon) | [177] | |
Daidzein, glycitein and genistein | Restraint stress-induced IBS-like alterations in rats | ↓ Colonic mast cell density | Estrogen receptor-mediated | [181] |
Green tea polyphenols | RBL-2H3 cells | ↓ Histamine release | Metabolic events associated to the elevation of intracellular Ca2+, inhibition of tyrosine phosphorylation of cellular proteins including pp125(FAK) | [185,186] |
Green tea polyphenols | RBL-2H3 cells BMMCs | ↓ β-hexosaminidase release ↓ LTC4 secretion | Changes in ROS production and mitochondrial membrane potential | [182] |
Green tea polyphenols (EGCG) | RBL-2H3 cells BMMCs | ↑ IL-13 production ↑ TNF-α production | SOC-dependent Ca2+ influx and ROS generation | [183] |
Compound | System | Effect a | Mechanism of Action | Reference |
---|---|---|---|---|
Curcumin | Intestinal mast cell-IgE-mediated inflammatory reaction model in rats | ↓ Rat chymase II | [133] | |
Curcumin | RBL-2H3 cells BMMCs | ↓ TNF-α expression and release ↓ IL-4 expression and release ↓ β –hexosaminidase release | Inhibition of Syk activity, inhibition of phosphorylation of Akt and MAPKs p38, p44/42 and JNK | [191] |
Curcumin | Passive cutaneous anaphylaxis model in mice | ↓ Mast cell-dependent passive cutaneous anaphylaxis responses (Evans blue extravasation) | [191] | |
Cinnamon extract/Cinnamaldehyde | Human intestinal mast cells RBL-2H3 cells | ↓ Tryptase expression ↓ β–hexosaminidase release ↓ cysLt release ↓ CXCL8 release ↓ CXCL8 expression ↓ CCL2 expression ↓ CCL3 expression ↓ CCL4 expression ↓ TNF-α expression | Inhibition of Akt and the MAPKs ERK, JNK, and p38; inhibition of PLCγ1 phosphorilation | [196,198] |
Cinnamon extract/Cinnamaldehyde | Mouse duodenal tissue | ↓ MCP6 and MC-CPA expression | [196] | |
Cinnamon extract/Cinnamaldehyde | Murine IL-10 knockout model of colitis | ↓ Proteases expression (MC-CPA, MCP-1 and MCP-4) ↓ Expression of pro-inflammatory mediators (CXCL8, CCL2, CCL3 and CCL4, IL-1β, TNF, INFγ) | Inhibition of NFκB signaling | [197] |
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Uranga, J.A.; Martínez, V.; Abalo, R. Mast Cell Regulation and Irritable Bowel Syndrome: Effects of Food Components with Potential Nutraceutical Use. Molecules 2020, 25, 4314. https://doi.org/10.3390/molecules25184314
Uranga JA, Martínez V, Abalo R. Mast Cell Regulation and Irritable Bowel Syndrome: Effects of Food Components with Potential Nutraceutical Use. Molecules. 2020; 25(18):4314. https://doi.org/10.3390/molecules25184314
Chicago/Turabian StyleUranga, José Antonio, Vicente Martínez, and Raquel Abalo. 2020. "Mast Cell Regulation and Irritable Bowel Syndrome: Effects of Food Components with Potential Nutraceutical Use" Molecules 25, no. 18: 4314. https://doi.org/10.3390/molecules25184314