論文 - 詳細
| RRC ID | 64991 |
|---|---|
| 著者 | Nakajima A, Oda S, Yokoi T. |
| タイトル | Allopurinol induces innate immune responses through mitogen-activated protein kinase signaling pathways in HL-60 cells. |
| ジャーナル | J Appl Toxicol |
| Abstract |
Allopurinol, an inhibitor of xanthine oxidase, is a frequent cause of severe cutaneous adverse reactions (SCARs) in humans, including drug rash with eosinophilia and systemic symptoms, Stevens-Johnson syndrome and toxic epidermal necrolysis. Although SCARs have been suspected to be immune-mediated, the mechanisms of allopurinol-induced SCARs remain unclear. In this study, we examined whether allopurinol has the ability to induce innate immune responses in vitro using human dendritic cell (DC)-like cell lines, including HL-60, THP-1 and K562, and a human keratinocyte cell line, HaCaT. In this study, we demonstrate that treatment of HL-60 cells with allopurinol significantly increased the mRNA expression levels of interleukin-8, monocyte chemotactic protein-1 and tumor necrosis factor α in a time- and concentration-dependent manner. Furthermore, allopurinol induced the phosphorylation of mitogen-activated protein kinases (MAPK), such as c-Jun N-terminal kinase and extracellular signal-regulated kinase, which regulate cytokine production in DC. In addition, allopurinol-induced increases in cytokine expression were inhibited by co-treatment with the MAPK inhibitors. Collectively, these results suggest that allopurinol has the ability to induce innate immune responses in a DC-like cell line through activation of the MAPK signaling pathways. These results indicate that innate immune responses induced by allopurinol might be involved in the development of allopurinol-induced SCARs. Copyright © 2015 John Wiley & Sons, Ltd. |
| 巻・号 | 36(9) |
| ページ | 1120-8 |
| 公開日 | 2016-9-1 |
| DOI | 10.1002/jat.3272 |
| PMID | 26641773 |
| MeSH | Allopurinol / toxicity* Chemokine CCL2 / genetics Chemokine CCL2 / metabolism Dendritic Cells / drug effects Dendritic Cells / immunology Dendritic Cells / metabolism Extracellular Signal-Regulated MAP Kinases / genetics Extracellular Signal-Regulated MAP Kinases / metabolism HL-60 Cells Humans Immunity, Innate / drug effects* Immunity, Innate / immunology Interleukin-8 / genetics Interleukin-8 / metabolism JNK Mitogen-Activated Protein Kinases / genetics JNK Mitogen-Activated Protein Kinases / metabolism K562 Cells Keratinocytes / cytology Keratinocytes / drug effects Keratinocytes / metabolism MAP Kinase Signaling System* Phosphorylation RNA, Messenger / genetics RNA, Messenger / metabolism Tumor Necrosis Factor-alpha / metabolism |
| IF | 2.997 |
| 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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| 最多言及媒体 | X(Twitter) |
| 各媒体での言及数の合計 | 1 |
| 過去6か月間でのオルトメトリクス指標の変動値 | 0.0 |
| リソース情報 | |
| ヒト・動物細胞 | THP-1(RCB1189) |