title: SG-HQ2 inhibits mast cell-mediated allergic inflammation through suppression of histamine release and pro-inflammatory cytokines.
abstract: In this study, we investigated the effect of 3,4,5-trihydroxy-N-(8-hydroxyquinolin-2-yl)benzamide) (SG-HQ2), a synthetic analogue of gallic acid (3,4,5-trihydroxybenzoic acid), on the mast cell-mediated allergic inflammation and the possible mechanism of action. Mast cells play major roles in immunoglobulin E-mediated allergic responses by the release of histamine, lipid-derived mediators, and pro-inflammatory cytokines. We previously reported the potential effects of gallic acid using allergic inflammation models. For incremental research, we synthesized the SG-HQ2 by the modification of functional groups from gallic acid. SG-HQ2 attenuated histamine release by the reduction of intracellular calcium in human mast cells and primary peritoneal mast cells. The inhibitory efficacy of SG-HQ2 was similar with gallic acid. Enhanced expression of pro-inflammatory cytokines such as tumor necrosis factor-α, interleukin-1β, interleukin-4, and interleukin-6 in activated mast cells was significantly diminished by SG-HQ2 100 times lower concentration of gallic acid. This inhibitory effect was mediated by the reduction of nuclear factor-κB. In animal models, SG-HQ2 inhibited compound 48/80-induced serum histamine release and immunoglobulin E-mediated local allergic reaction, passive cutaneous anaphylaxis. Our results indicate that SG-HQ2, an analogue of gallic acid, might be a possible therapeutic candidate for mast cell-mediated allergic inflammatory diseases through suppression of histamine release and pro-inflammatory cytokines.
authors.affiliation: CMRI, BK21 Plus KNU Biomedical Convergence Program, Department of Pharmacology, School of Medicine, Kyungpook National University, Daegu 700-422, Republic of Korea.
authors.forename: In-Gyu
authors.initials: IG
authors.lastname: Je
authors.affiliation: CMRI, BK21 Plus KNU Biomedical Convergence Program, Department of Pharmacology, School of Medicine, Kyungpook National University, Daegu 700-422, Republic of Korea.
authors.forename: Hui-Hun
authors.initials: HH
authors.lastname: Kim
authors.affiliation: College of Pharmacy, Yeungnam University, Gyeongbuk 712-749, Republic of Korea.
authors.forename: Pil-Hoon
authors.initials: PH
authors.lastname: Park
authors.affiliation: Department of Immunology, Keimyung University, Daegu 704-701, Republic of Korea.
authors.forename: Taeg Kyu
authors.initials: TK
authors.lastname: Kwon
authors.affiliation: College of Pharmacy, Gachon University, Incheon 406-840, Republic of Korea shkim72@knu.ac.kr syseo@gachon.ac.kr tyshin@woosuk.ac.kr.
authors.forename: Seung-Yong
authors.initials: SY
authors.lastname: Seo
authors.affiliation: College of Pharmacy, Woosuk University, Jeonju 565-701, Republic of Korea shkim72@knu.ac.kr syseo@gachon.ac.kr tyshin@woosuk.ac.kr.
authors.forename: Tae-Yong
authors.initials: TY
authors.lastname: Shin
authors.affiliation: CMRI, BK21 Plus KNU Biomedical Convergence Program, Department of Pharmacology, School of Medicine, Kyungpook National University, Daegu 700-422, Republic of Korea shkim72@knu.ac.kr syseo@gachon.ac.kr tyshin@woosuk.ac.kr.
authors.forename: Sang-Hyun
authors.initials: SH
authors.lastname: Kim
mesh_terms: D000818:Animals; D002118:Calcium / Q000378:metabolism; D016207:Cytokines / Q000378:metabolism*; D005707:Gallic Acid / Q000031:analogs & derivatives* / Q000494:pharmacology; D006636:Histamine Release / Q000187:drug effects*; D006912:Hydroxyquinolines / Q000494:pharmacology*; D006967:Hypersensitivity / Q000517:prevention & control*; D007073:Immunoglobulin E / Q000008:administration & dosage; D007249:Inflammation / Q000517:prevention & control*; D018836:Inflammation Mediators / Q000378:metabolism*; D008297:Male; D008407:Mast Cells / Q000187:drug effects* / Q000378:metabolism; D051379:Mice; D016328:NF-kappa B / Q000378:metabolism; D010323:Passive Cutaneous Anaphylaxis; D051381:Rats; D017207:Rats, Sprague-Dawley; D060888:Real-Time Polymerase Chain Reaction
chemical_list: D016207:Cytokines; D006912:Hydroxyquinolines; D018836:Inflammation Mediators; D016328:NF-kappa B; C000599965:SG-HQ2; D007073:Immunoglobulin E; D005707:Gallic Acid; D002118:Calcium
keywords: Allergic inflammation; histamine; mast cells; pro-inflammatory cytokine