title: Inhibition of allergic inflammation by supplementation with 5-hydroxytryptophan.
abstract: Clinical reports indicate that patients with allergy/asthma commonly have associated symptoms of anxiety/depression. Anxiety/depression can be reduced by 5-hydroxytryptophan (5-HTP) supplementation. However, it is not known whether 5-HTP reduces allergic inflammation. Therefore, we determined whether 5-HTP supplementation reduces allergic inflammation. We also determined whether 5-HTP decreases passage of leukocytes through the endothelial barrier by regulating endothelial cell function. For these studies, C57BL/6 mice were supplemented with 5-HTP, treated with ovalbumin fraction V (OVA), house dust mite (HDM) extract, or IL-4, and examined for allergic lung inflammation and OVA-induced airway responsiveness. To determine whether 5-HTP reduces leukocyte or eosinophil transendothelial migration, endothelial cells were pretreated with 5-HTP, washed and then used in an in vitro transendothelial migration assay under laminar flow. Interestingly, 5-HTP reduced allergic lung inflammation by 70-90% and reduced antigen-induced airway responsiveness without affecting body weight, blood eosinophils, cytokines, or chemokines. 5-HTP reduced allergen-induced transglutaminase 2 (TG2) expression and serotonylation (serotonin conjugation to proteins) in lung endothelial cells. Consistent with the regulation of endothelial serotonylation in vivo, in vitro pretreatment of endothelial cells with 5-HTP reduced TNF-α-induced endothelial cell serotonylation and reduced leukocyte transendothelial migration. Furthermore, eosinophil and leukocyte transendothelial migration was reduced by inhibitors of transglutaminase and by inhibition of endothelial cell serotonin synthesis, suggesting that endothelial cell serotonylation is key for leukocyte transendothelial migration. In summary, 5-HTP supplementation inhibits endothelial serotonylation, leukocyte recruitment, and allergic inflammation. These data identify novel potential targets for intervention in allergy/asthma.
authors: Division of Allergy-Immunology, Northwestern Univeristy Feinberg School of Medicine, Chicago, IL 60611, USA.
authors: Hiam
authors: H
authors: Abdala-Valencia
authors: Sergejs
authors: S
authors: Berdnikovs
authors: Christine A
authors: CA
authors: McCary
authors: Daniela
authors: D
authors: Urick
authors: Riti
authors: R
authors: Mahadevia
authors: Michelle E
authors: ME
authors: Marchese
authors: Kelsey
authors: K
authors: Swartz
authors: Lakiea
authors: L
authors: Wright
authors: Gökhan M
authors: GM
authors: Mutlu
authors: Joan M
authors: JM
authors: Cook-Mills
mesh_terms: D006916:5-Hydroxytryptophan / Q000276:immunology / Q000493:pharmacokinetics*; D000818:Animals; D018687:Antidepressive Agents, Second-Generation / Q000276:immunology / Q000493:pharmacokinetics; D001249:Asthma / Q000188:drug therapy / Q000276:immunology; D015815:Cell Adhesion Molecules / Q000378:metabolism; D002460:Cell Line; D002465:Cell Movement / Q000187:drug effects / Q000276:immunology; D018925:Chemokines / Q000378:metabolism; D004195:Disease Models, Animal; D042783:Endothelial Cells / Q000166:cytology / Q000276:immunology; D005260:Female; D006967:Hypersensitivity / Q000188:drug therapy* / Q000276:immunology*; D007165:Immunosuppression Therapy / Q000379:methods*; D015847:Interleukin-4 / Q000276:immunology / Q000494:pharmacology; D007962:Leukocytes / Q000166:cytology / Q000187:drug effects / Q000276:immunology; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D010047:Ovalbumin / Q000276:immunology / Q000494:pharmacology; D039981:Pyroglyphidae / Q000276:immunology; D012701:Serotonin / Q000276:immunology / Q000378:metabolism; D013154:Spleen / Q000166:cytology
chemical_list: D018687:Antidepressive Agents, Second-Generation; D015815:Cell Adhesion Molecules; D018925:Chemokines; D015847:Interleukin-4; D012701:Serotonin; D010047:Ovalbumin; D006916:5-Hydroxytryptophan