論文 - 詳細
RRC ID | 63634 |
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著者 | Shishido K, Kuroishi T, Sugawara S. |
タイトル | P2 purinergic receptor signaling and interleukin-1 synergistically induce interleukin-6 production in a human oral squamous carcinoma cell line. |
ジャーナル | J Oral Biosci |
Abstract |
OBJECTIVES:The aim of this study was to investigate the inflammatory roles of P2 purinergic receptor (P2R) signaling in oral squamous cell carcinoma (OSCC). METHODS:Human OSCC cell lines HSC-2, Ca9-22, and HO-1-u-1 were stimulated with P2R agonists. The concentration of interleukin (IL)-6 in culture supernatants was measured using an enzyme-linked immune sorbent assay. Expression levels of messenger RNAs (mRNAs) were analyzed using reverse transcription polymerase chain reaction. Phosphorylation of intracellular signaling molecules was analyzed using western blotting. RESULTS:HSC-2 cells expressed the mRNAs for P2X4-6 and all P2YRs. ATP or ADP induced significantly greater production of IL-6 by HSC-2 cells. Ca9-22 cells expressed mRNAs for P2X4-6 and all P2YRs except P2Y4. ATP or ADP induced the production of IL-6 by Ca9-22 cells, but the IL-6 concentration was much lower than that in HSC-2 cells. Although Ho-1-u-1 cells expressed the mRNAs for P2X4-6 and all P2YRs, ATP or ADP did not induce IL-6 production. The production of IL-6 by HSC-2 cells stimulated with adenine nucleotides was significantly inhibited by P2R antagonists and a p38 mitogen-activated protein kinase inhibitor, but not by extracellular signal-related kinase or c-Jun N-terminal kinase inhibitors. The proinflammatory cytokine IL-1 significantly augmented P2R-induced IL-6 production by HSC-2 cells via the nuclear factor-κB signaling pathway. CONCLUSIONS:The present study suggests that P2Rs signaling and IL-1 synergistically induce chronic inflammation in OSCC. Because chronic inflammation is a well-known driving force of tumor progression, these results support therapeutic strategies that target P2Rs signaling in OSCC. |
巻・号 | 63(1) |
ページ | 80-90 |
公開日 | 2021-3-1 |
DOI | 10.1016/j.job.2021.01.004 |
PII | S1349-0079(21)00008-6 |
PMID | 33497843 |
MeSH | Carcinoma, Squamous Cell* Cell Line Cells, Cultured Humans Interleukin-1 Interleukin-6 / genetics Mouth Neoplasms* |
リソース情報 | |
ヒト・動物細胞 | HSC-2(RCB1945), HO-1-u-1(RCB2102) |