title: FICZ, a tryptophan photoproduct, suppresses pulmonary eosinophilia and Th2-type cytokine production in a mouse model of ovalbumin-induced allergic asthma.
abstract: Most studies about functions of aryl hydrocarbon receptor (AhR) in the pathogenesis of asthma have been carried out with non-physiological industrial by-products such as 2,3,7,8-tetrachlorodibenzo-p-dioxin and benzo(a)pyrene. In the present study, effects of 6-formylindolo[3,2-b]carbazole (FICZ), a tryptophan photoproduct postulated as a candidate physiological ligand of AhR, on the pathogenesis of asthma were examined and then underlying mechanisms of its immumodulatory effects were investigated. FICZ significantly reduced pulmonary eosinophilia and Th2 cytokine expression in the lungs. Flow cytometric analysis of mediastinal lymph nodes showed that IL-4 producing cells decreased in FICZ-treated mice compared with PBS control. Next, effects of FICZ on in vitro Th2 differentiation and expression of the Th2 transcription factor GATA-3 were examined. CD4+ T cells were isolated from the spleen and incubated under the Th2 differentiation conditions. FICZ inhibited both Th2 differentiation and the expression of GATA-3. Finally, activation of STAT6, which is necessary for Th2 differentiation, was inhibited by FICZ.
authors.affiliation: Department of Biology, Changwon National University, Changwon, Kyungnam 641-773, Korea.
authors.forename: Kyu-Tae
authors.initials: KT
authors.lastname: Jeong
authors.forename: Sung-Jun
authors.initials: SJ
authors.lastname: Hwang
authors.forename: Gap-Soo
authors.initials: GS
authors.lastname: Oh
authors.forename: Joo-Hung
authors.initials: JH
authors.lastname: Park
mesh_terms: D000818:Animals; D018926:Anti-Allergic Agents / Q000008:administration & dosage / Q000009:adverse effects; D001249:Asthma / Q000150:complications / Q000188:drug therapy* / Q000276:immunology; D002227:Carbazoles / Q000008:administration & dosage* / Q000009:adverse effects / Q000494:pharmacology; D002478:Cells, Cultured; D016207:Cytokines / Q000235:genetics / Q000378:metabolism*; D004195:Disease Models, Animal; D050990:GATA3 Transcription Factor / Q000235:genetics / Q000378:metabolism; D005786:Gene Expression Regulation / Q000187:drug effects; D006801:Humans; D007165:Immunosuppression Therapy; D008024:Ligands; D051379:Mice; D008807:Mice, Inbred BALB C; D010047:Ovalbumin / Q000276:immunology; D011657:Pulmonary Eosinophilia / Q000188:drug therapy* / Q000276:immunology; D018336:Receptors, Aryl Hydrocarbon / Q000819:agonists; D018418:Th2 Cells / Q000187:drug effects / Q000276:immunology*; D014364:Tryptophan / Q000378:metabolism
chemical_list: C111855:6-formylindolo(3,2-b)carbazole; D018926:Anti-Allergic Agents; D002227:Carbazoles; D016207:Cytokines; D050990:GATA3 Transcription Factor; D008024:Ligands; D018336:Receptors, Aryl Hydrocarbon; D014364:Tryptophan; D010047:Ovalbumin