title: 2-Hydroxy-3-methoxybenzoic acid attenuates mast cell-mediated allergic reaction in mice via modulation of the FcεRI signaling pathway.
abstract: Mast cells are important effector cells in immunoglobulin (Ig) E-mediated allergic reactions such as asthma, atopic dermatitis and rhinitis. Vanillic acid, a natural product, has shown anti-oxidant and anti-inflammatory activities. In the present study, we investigated the anti-allergic inflammatory effects of ortho-vanillic acid (2-hydroxy-3-methoxybenzoic acid, o-VA) that was a derivative of vanillic acid isolated from Amomum xanthioides. In mouse anaphylaxis models, oral administration of o-VA (2, 10, 50 mg/kg) dose-dependently attenuated ovalbumin-induced active systemic anaphylaxis and IgE-mediated cutaneous allergic reactions such as hypothermia, histamine release, IgE production and vasodilation; administration of o-VA also suppressed the mast cell degranulator compound 48/80-induced anaphylaxis. In cultured mast cell line RBL-2H3 and isolated rat peritoneal mast cells in vitro, pretreatment with o-VA (1-100 μmol/L) dose-dependently inhibited DNP-HSA-induced degranulation of mast cells by decreasing the intracellular free calcium level, and suppressed the expression of pro-inflammatory cytokines TNF-α and IL-4. Pretreatment of RBL-2H3 cells with o-VA suppressed DNP-HSA-induced phosphorylation of Lyn, Syk, Akt, and the nuclear translocation of nuclear factor-κB. In conclusion, o-VA suppresses the mast cell-mediated allergic inflammatory response by blocking the signaling pathways downstream of high affinity IgE receptor (FcεRI) on the surface of mast cells.
authors.affiliation: CMRI, Department of Pharmacology, Daegu 700-422, Republic of Korea.
authors.forename: Yeon-Yong
authors.initials: YY
authors.lastname: Kim
authors.affiliation: CMRI, Department of Pharmacology, Daegu 700-422, Republic of Korea.|Department of Molecular Medicine, Daegu 700-422, Republic of Korea.
authors.forename: In-Gyu
authors.initials: IG
authors.lastname: Je
authors.affiliation: CMRI, Department of Pharmacology, Daegu 700-422, Republic of Korea.
authors.forename: Min Jong
authors.initials: MJ
authors.lastname: Kim
authors.affiliation: CMRI, Department of Pharmacology, Daegu 700-422, Republic of Korea.
authors.forename: Byeong-Cheol
authors.initials: BC
authors.lastname: Kang
authors.affiliation: CMRI, Department of Pharmacology, Daegu 700-422, Republic of Korea.
authors.forename: Young-Ae
authors.initials: YA
authors.lastname: Choi
authors.affiliation: Department of Biochemistry and Cell Biology, School of Medicine, Kyungpook National University, Daegu 700-422, Republic of Korea.
authors.forename: Moon-Chang
authors.initials: MC
authors.lastname: Baek
authors.affiliation: Research Laboratories, ILDONG Pharmaceutical Co Ltd, Hwaseong 18449, Republic of Korea.
authors.forename: Byungheon
authors.initials: B
authors.lastname: Lee
authors.affiliation: CMRI, Department of Pharmacology, Daegu 700-422, Republic of Korea.|Molecular Immunology Section, Laboratory of Immunology, National Eye Institute, National Institutes of Health, Bethesda, MD 20892, USA.
authors.forename: Jin Kyeong
authors.initials: JK
authors.lastname: Choi
authors.affiliation: College of Pharmacy, Woosuk University, Jeonju 565-701, Republic of Korea.
authors.forename: Hae Ran
authors.initials: HR
authors.lastname: Park
authors.affiliation: College of Pharmacy, Woosuk University, Jeonju 565-701, Republic of Korea.
authors.forename: Tae-Yong
authors.initials: TY
authors.lastname: Shin
authors.affiliation: Natural Product Research Center, Korea Research Institute of Bioscience and Biotechnology, Jeongeup 580-185, Republic of Korea.
authors.forename: Soyoung
authors.initials: S
authors.lastname: Lee
authors.affiliation: National Primate Research Center, Korea Research Institute of Bioscience and Biotechnology, Ochang 28116, Republic of Korea.
authors.forename: Seung-Bin
authors.initials: SB
authors.lastname: Yoon
authors.affiliation: National Primate Research Center, Korea Research Institute of Bioscience and Biotechnology, Ochang 28116, Republic of Korea.
authors.forename: Sang-Rae
authors.initials: SR
authors.lastname: Lee
authors.affiliation: Department of Molecular Medicine, School of Medicine, Gachon University, Incheon 406-840, Republic of Korea.
authors.forename: Dongwoo
authors.initials: D
authors.lastname: Khang
authors.affiliation: CMRI, Department of Pharmacology, Daegu 700-422, Republic of Korea.
authors.forename: Sang-Hyun
authors.initials: SH
authors.lastname: Kim
mesh_terms: D000707:Anaphylaxis / Q000139:chemically induced / Q000188:drug therapy* / Q000276:immunology*; D000818:Animals; D001565:Benzoates / Q000494:pharmacology* / Q000627:therapeutic use*; D002118:Calcium / Q000378:metabolism; D015550:Cell Degranulation / Q000187:drug effects; D002478:Cells, Cultured; D004140:Dinitrophenols / Q000037:antagonists & inhibitors; D004305:Dose-Response Relationship, Drug; D006967:Hypersensitivity / Q000188:drug therapy* / Q000276:immunology; D007073:Immunoglobulin E / Q000187:drug effects; D018836:Inflammation Mediators / Q000378:metabolism; D008297:Male; D008407:Mast Cells / Q000187:drug effects* / Q000276:immunology; D051379:Mice; D016328:NF-kappa B / Q000378:metabolism; D010047:Ovalbumin / Q000037:antagonists & inhibitors; D010766:Phosphorylation / Q000187:drug effects; D051381:Rats; D017455:Receptors, IgE / Q000037:antagonists & inhibitors / Q000276:immunology*; D012709:Serum Albumin / Q000037:antagonists & inhibitors; D015398:Signal Transduction / Q000187:drug effects; D014641:Vanillic Acid / Q000031:analogs & derivatives*; D003189:p-Methoxy-N-methylphenethylamine / Q000037:antagonists & inhibitors
chemical_list: C000621631:2-hydroxy-3-methoxybenzoic acid; D001565:Benzoates; D004140:Dinitrophenols; C553474:FCER1A protein, rat; D018836:Inflammation Mediators; D016328:NF-kappa B; D017455:Receptors, IgE; D012709:Serum Albumin; C058064:dinitrophenyl-human serum albumin conjugate; D007073:Immunoglobulin E; D003189:p-Methoxy-N-methylphenethylamine; D010047:Ovalbumin; D014641:Vanillic Acid; D002118:Calcium