%0 Journal Article %T 2-Hydroxy-3-methoxybenzoic acid attenuates mast cell-mediated allergic reaction in mice via modulation of the Fc¦ÅRI signaling pathway %A Byeong-Cheol Kang %A Byungheon Lee %A Dongwoo Khang %A Hae Ran Park %A In-Gyu Je %A Jin Kyeong Choi %A Min Jong Kim %A Moon-Chang Baek %A Sang-Rae Lee %A Seung-Bin Yoon %A Soyoung Lee %A Tae-Yong Shin %A Yeon-Yong Kim %A Young-Ae Choi %J Archive of "Acta Pharmacologica Sinica". %D 2017 %R 10.1038/aps.2016.112 %X 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¨C100 ¦Ìmol/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-¦Á 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-¦ÊB. In conclusion, o-VA suppresses the mast cell-mediated allergic inflammatory response by blocking the signaling pathways downstream of high affinity IgE receptor (Fc¦ÅRI) on the surface of mast cells %K type I hypersensitivity %K allergic inflammation %K o-vanillic acid %K histamine %K pro-inflammatory cytokine %K high affinity IgE receptor %K RBL-2H3 cells %K rat peritoneal mast cells %U https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5220539/