論文 - 詳細
| RRC ID | 42663 |
|---|---|
| 著者 | Rokudai A, Terui Y, Kuniyoshi R, Mishima Y, Mishima Y, Aizu-Yokota E, Sonoda Y, Kasahara T, Hatake K. |
| タイトル | Differential regulation of eotaxin-1/CCL11 and eotaxin-3/CCL26 production by the TNF-alpha and IL-4 stimulated human lung fibroblast. |
| ジャーナル | Biol Pharm Bull |
| Abstract |
Allergic asthma and allergic dermatitis are chronic inflammatory diseases and are characterized by an accumulation of eosinophils at sites of inflammation. Eotaxin-1/CCL11 and eotaxin-3/CCL26 are members of the CC chemokine family, which are known to be potent chemoattractants for eosinophils. We observed that a human lung fibroblast, HFL-1 produces eotaxin-1 and -3 in response to TNF-alpha plus IL-4 stimulation, accompanied with NF-kappaB and STAT6 activation. We explored which signaling pathways are operative in the production of eotaxin-1 and -3 using several inhibitors. Eotaxin-1/CCL11 production was inhibited by a p38 mitogen-activated protein kinase (MAPK) inhibitor, SB203580, but not by the MEK (MAPK/ERK kinase) inhibitors, PD98059 and U0126. In contrast, eotaxin-3/CCL26 production was inhibited similarly by PD98059 as well as U0126 and SB203580. In addition, two proteasome inhibitors, N-acetyl-leucyl-leucyl-norleucinal (ALLN) and bortezomib with significant inhibitory activity on NF-kappaB activation, inhibited eotaxin-1/CCL11 production with IC50 8 microM for ALLN and IC50 16 nM for bortezomib. In contrast, eotaxin-3/CCL26 production was not inhibited significantly up to 10 microM of ALLN (IC50 16 microM) and up to 10 nM of bortezomib (IC50 11 nM), giving inhibition of eotaxin-3/CCL26 less sensitive than eotaxin-1/CCL11 production by the proteasome inhibitors. Synergistic inhibition was observed among lower doses of SB203580 and proteasome inhibitors, particularly in the eotaxin-1/CCL11 production. No such prominent synergism was found on the eotaxin-3/CCL26 production. The suppression of eotaxin family production by these inhibitors may be efficacious against allergic diseases. |
| 巻・号 | 29(6) |
| ページ | 1102-9 |
| 公開日 | 2006-6-1 |
| DOI | 10.1248/bpb.29.1102 |
| PII | JST.JSTAGE/bpb/29.1102 |
| PMID | 16755001 |
| MeSH | Asthma / immunology Boronic Acids / pharmacology Bortezomib Cell Line Chemokine CCL11 / antagonists & inhibitors Chemokine CCL11 / biosynthesis* Chemokine CCL11 / immunology Chemokine CCL26 Chemokines, CC / antagonists & inhibitors Chemokines, CC / biosynthesis* Chemokines, CC / immunology Drug Synergism Enzyme Inhibitors / pharmacology Fibroblasts / drug effects* Fibroblasts / immunology Humans Hypersensitivity / immunology Immunoblotting Interleukin-4 / immunology Interleukin-4 / pharmacology* Interleukin-4 / physiology Leupeptins / pharmacology Lung / cytology Lung / drug effects* Lung / immunology Mitogen-Activated Protein Kinases / antagonists & inhibitors NF-kappa B / metabolism Pyrazines / pharmacology Recombinant Proteins / immunology Recombinant Proteins / pharmacology STAT6 Transcription Factor / metabolism Tumor Necrosis Factor-alpha / immunology Tumor Necrosis Factor-alpha / pharmacology* Tumor Necrosis Factor-alpha / physiology |
| IF | 1.863 |
| 引用数 | 28 |
| WOS 分野 | PHARMACOLOGY & PHARMACY |
| オルトメトリクス指標 |
オルトメトリクス指標項目
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| 各媒体での言及数の合計 | 0 |
| リソース情報 | |
| ヒト・動物細胞 | |