title: Tyrosol Suppresses Allergic Inflammation by Inhibiting the Activation of Phosphoinositide 3-Kinase in Mast Cells.
abstract: Allergic diseases such as atopic dermatitis, rhinitis, asthma, and anaphylaxis are attractive research areas. Tyrosol (2-(4-hydroxyphenyl)ethanol) is a polyphenolic compound with diverse biological activities. In this study, we investigated whether tyrosol has anti-allergic inflammatory effects. Ovalbumin-induced active systemic anaphylaxis and immunoglobulin E-mediated passive cutaneous anaphylaxis models were used for the immediate-type allergic responses. Oral administration of tyrosol reduced the allergic symptoms of hypothermia and pigmentation in both animal models. Mast cells that secrete allergic mediators are key regulators on allergic inflammation. Tyrosol dose-dependently decreased mast cell degranulation and expression of inflammatory cytokines. Intracellular calcium levels and activation of inhibitor of κB kinase (IKK) regulate cytokine expression and degranulation. Tyrosol blocked calcium influx and phosphorylation of the IKK complex. To define the molecular target for tyrosol, various signaling proteins involved in mast cell activation such as Lyn, Syk, phosphoinositide 3-kinase (PI3K), and Akt were examined. Our results showed that PI3K could be a molecular target for tyrosol in mast cells. Taken together, these findings indicated that tyrosol has anti-allergic inflammatory effects by inhibiting the degranulation of mast cells and expression of inflammatory cytokines; these effects are mediated via PI3K. Therefore, we expect tyrosol become a potential therapeutic candidate for allergic inflammatory disorders.
authors.affiliation: 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: Department of Thoracic and Cardiovascular Surgery, CHA Gumi Medical Center, CHA University, Gumi 730-040, Republic of Korea.
authors.forename: Duk-Sil
authors.initials: DS
authors.lastname: Kim
authors.affiliation: Department of Thoracic and Cardiovascular Surgery, CHA Gumi Medical Center, CHA University, Gumi 730-040, Republic of Korea.
authors.forename: Sung-Wan
authors.initials: SW
authors.lastname: Kim
authors.affiliation: Department of Pharmacology, School of Medicine, Kyungpook National University, Daegu 700-422, Republic of Korea.
authors.forename: Soyoung
authors.initials: S
authors.lastname: Lee
authors.affiliation: School of Life Sciences, Kyungpook National University, Daegu 702-701, Republic of Korea.
authors.forename: Hyun-Shik
authors.initials: HS
authors.lastname: Lee
authors.affiliation: Department of Oral Pathology and Regenerative Medicine, School of Dentistry, Kyungpook National University, Daegu 700-412, Republic of Korea.
authors.forename: Eui Kyun
authors.initials: EK
authors.lastname: Park
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: Department of Pharmacology, School of Medicine, Kyungpook National University, Daegu 700-422, Republic of Korea.
authors.forename: Sang-Hyun
authors.initials: SH
authors.lastname: Kim
mesh_terms: D000818:Animals; D018926:Anti-Allergic Agents / Q000494:pharmacology; D000893:Anti-Inflammatory Agents / Q000494:pharmacology; D000975:Antioxidants / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects; D015153:Blotting, Western; D015550:Cell Degranulation / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects; D002478:Cells, Cultured; D016207:Cytokines / Q000235:genetics / Q000378:metabolism; D004789:Enzyme Activation / Q000187:drug effects; D004797:Enzyme-Linked Immunosorbent Assay; D006967:Hypersensitivity / Q000201:enzymology / Q000276:immunology / Q000517:prevention & control*; D007249:Inflammation / Q000201:enzymology / Q000276:immunology / Q000517:prevention & control*; D008297:Male; D008407:Mast Cells / Q000187:drug effects / Q000201:enzymology / Q000276:immunology*; D051379:Mice; D010323:Passive Cutaneous Anaphylaxis / Q000187:drug effects* / Q000276:immunology; D010626:Phenylethyl Alcohol / Q000031:analogs & derivatives* / Q000494:pharmacology; D000081082:Phosphoinositide-3 Kinase Inhibitors; D010766:Phosphorylation / Q000187:drug effects; D012333:RNA, Messenger / Q000235:genetics; D051381:Rats; D017207:Rats, Sprague-Dawley; D060888:Real-Time Polymerase Chain Reaction; D020133:Reverse Transcriptase Polymerase Chain Reaction
chemical_list: D018926:Anti-Allergic Agents; D000893:Anti-Inflammatory Agents; D000975:Antioxidants; D016207:Cytokines; D000081082:Phosphoinositide-3 Kinase Inhibitors; D012333:RNA, Messenger; C011867:4-hydroxyphenylethanol; D010626:Phenylethyl Alcohol