論文 - 詳細
| RRC ID | 18989 |
|---|---|
| 著者 | Mizuno K, Fukami T, Toyoda Y, Nakajima M, Yokoi T. |
| タイトル | Terbinafine stimulates the pro-inflammatory responses in human monocytic THP-1 cells through an ERK signaling pathway. |
| ジャーナル | Life Sci |
| Abstract |
AIMS:Oral antifungal terbinafine has been reported to cause liver injury with inflammatory responses in a small percentage of patients. However the underlying mechanism remains unknown. To examine the inflammatory reactions, we investigated whether terbinafine and other antifungal drugs increase the release of pro-inflammatory cytokines using human monocytic cells. MAIN METHODS:Dose- and time-dependent changes in the mRNA expression levels and the release of interleukin (IL)-8 and tumor necrosis factor (TNF)α from human monocytic THP-1 and HL-60 cells with antifungal drugs were measured. Effects of terbinafine on the phosphorylation of extracellular signal-regulated kinase (ERK)1/2, p38 mitogen-activated protein (MAP) kinase and c-Jun N-terminal kinase (JNK)1/2 were investigated. KEY FINDINGS:The release of IL-8 and TNFα from THP-1 and HL-60 cells was significantly increased by treatment with terbinafine but not by fluconazole, suggesting that terbinafine can stimulate monocytes and increase the pro-inflammatory cytokine release. Terbinafine also significantly increased the phosphorylation of ERK1/2 and p38 MAP kinase in THP-1 cells. Pretreatment with a MAP kinase/ERK kinase (MEK)1/2 inhibitor U0126 significantly suppressed the increase of IL-8 and TNFα levels by terbinafine treatment in THP-1 cells, but p38 MAPK inhibitor SB203580 did not. These results suggested that an ERK1/2 pathway plays an important role in the release of IL-8 and TNFα in THP-1 cells treated with terbinafine. SIGNIFICANCE:The release of inflammatory mediators by terbinafine might be one of the mechanisms underlying immune-mediated liver injury. This in vitro method may be useful to predict adverse inflammatory reactions that lead to drug-induced liver injury. |
| 巻・号 | 87(17-18) |
| ページ | 537-44 |
| 公開日 | 2010-10-23 |
| DOI | 10.1016/j.lfs.2010.08.010 |
| PII | S0024-3205(10)00373-5 |
| PMID | 20816994 |
| MeSH | Antifungal Agents / pharmacology Chemokines / biosynthesis Chemokines / genetics Chemokines / metabolism Cytokines / biosynthesis Cytokines / genetics Cytokines / metabolism Dose-Response Relationship, Drug Extracellular Signal-Regulated MAP Kinases / metabolism Extracellular Signal-Regulated MAP Kinases / physiology* HL-60 Cells Humans Inflammation Mediators / metabolism* Inflammation Mediators / physiology MAP Kinase Signaling System / drug effects* MAP Kinase Signaling System / physiology Monocytes / drug effects* Monocytes / enzymology* Monocytes / metabolism Naphthalenes / pharmacology* Terbinafine |
| IF | 3.647 |
| 引用数 | 14 |
| WOS 分野 | MEDICINE, RESEARCH & EXPERIMENTAL PHARMACOLOGY & PHARMACY |
| リソース情報 | |
| ヒト・動物細胞 | THP-1(RCB1189) |