title: Diesel exhaust particles upregulate eotaxin gene expression in human bronchial epithelial cells via nuclear factor-kappa B-dependent pathway.
abstract: Fine particles derived from diesel engines, diesel exhaust particles (DEP), have been shown to augment gene expression of several inflammatory cytokines in human airway epithelial cells in vitro. However, it remains unclear whether or not DEP have any effect on the expression and production of eotaxin, an important chemokine involved in eosinophil recruitment into the airways. We studied the effects of DEP by using a conventional suspended DEP and by a recently established in vitro cell exposure system to diesel exhaust (Abe S, Takizawa H, Sugawara I, and Kudoh S, Am J Respir Cell Mol Biol 22: 296-303, 2000). DEP showed a dose-dependent stimulatory effect on eotaxin production by normal human peripheral airway epithelial cells as well as by bronchial epithelial cell line BET-1A as assessed by specific ELISA. mRNA levels increased by DEP were shown by RT-PCR. DEP showed an additive effect on IL-13-stimulated eotaxin expression. DEP induced NF-kappaB activation by EMSA as previously reported but did not induce signal transducer and activator of transcription (STAT) 6 activation according to Western blot analysis. Finally, antioxidant agents (N-acetyl cysteine and pyrrolidine dithiocarbamate), which inhibited NF-kappaB activation but failed to affect STAT6 activation, almost completely attenuated DEP-induced eotaxin production, whereas these agents failed to attenuate IL-13-induced eotaxin production. These findings suggested that DEP stimulated eotaxin gene expression via NF-kappaB-dependent, but STAT6-independent, pathways.
authors.affiliation: Departments of Laboratory Medicine and Respiratory Medicine, Graduate School of Medicine, University of Tokyo, Tokyo 113-8655, Japan. takizawa-phy@h.u-tokyo.ac.jp
authors.forename: Hajime
authors.initials: H
authors.lastname: Takizawa
authors.forename: Shinji
authors.initials: S
authors.lastname: Abe
authors.forename: Hitoshi
authors.initials: H
authors.lastname: Okazaki
authors.forename: Tadashi
authors.initials: T
authors.lastname: Kohyama
authors.forename: Isamu
authors.initials: I
authors.lastname: Sugawara
authors.forename: Yoshinobu
authors.initials: Y
authors.lastname: Saito
authors.forename: Takayuki
authors.initials: T
authors.lastname: Ohtoshi
authors.forename: Shin
authors.initials: S
authors.lastname: Kawasaki
authors.forename: Masashi
authors.initials: M
authors.lastname: Desaki
authors.forename: Kazuhiko
authors.initials: K
authors.lastname: Nakahara
authors.forename: Kazuhiko
authors.initials: K
authors.lastname: Yamamoto
authors.forename: Kouji
authors.initials: K
authors.lastname: Matsushima
authors.forename: Mitsuru
authors.initials: M
authors.lastname: Tanaka
authors.forename: Masaru
authors.initials: M
authors.lastname: Sagai
authors.forename: Shoji
authors.initials: S
authors.lastname: Kudoh
mesh_terms: D000111:Acetylcysteine / Q000494:pharmacology; D000906:Antibodies; D000975:Antioxidants / Q000494:pharmacology; D001980:Bronchi / Q000166:cytology / Q000378:metabolism; D002478:Cells, Cultured; D054413:Chemokine CCL11; D019742:Chemokines, CC / Q000235:genetics* / Q000276:immunology; D024202:Electrophoretic Mobility Shift Assay; D004847:Epithelial Cells / Q000187:drug effects* / Q000378:metabolism; D005100:Expectorants / Q000494:pharmacology; D015870:Gene Expression / Q000187:drug effects; D006801:Humans; D066298:In Vitro Techniques; D018793:Interleukin-13 / Q000378:metabolism; D016328:NF-kappa B / Q000378:metabolism*; D011392:Proline / Q000031:analogs & derivatives* / Q000494:pharmacology; D012333:RNA, Messenger / Q000032:analysis; D020545:Respiratory Mucosa / Q000166:cytology / Q000378:metabolism*; D050800:STAT6 Transcription Factor; D015398:Signal Transduction / Q000187:drug effects; D013859:Thiocarbamates / Q000494:pharmacology; D015534:Trans-Activators / Q000378:metabolism; D015854:Up-Regulation / Q000187:drug effects; D001335:Vehicle Emissions / Q000009:adverse effects*
chemical_list: D000906:Antibodies; D000975:Antioxidants; C515456:CCL11 protein, human; D054413:Chemokine CCL11; D019742:Chemokines, CC; D005100:Expectorants; D018793:Interleukin-13; D016328:NF-kappa B; D012333:RNA, Messenger; D050800:STAT6 Transcription Factor; C494101:STAT6 protein, human; D013859:Thiocarbamates; D015534:Trans-Activators; D001335:Vehicle Emissions; C066229:prolinedithiocarbamate; D011392:Proline; D000111:Acetylcysteine