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
リソース情報
ヒト・動物細胞 THP-1(RCB1189)