P2 purinergic receptor signaling and interleukin-1 synergistically induce interleukin-6 production in a human oral squamous carcinoma cell line.
J Oral Biosci
; 63(1): 80-90, 2021 03.
Article
em En
| MEDLINE
| ID: mdl-33497843
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.Palavras-chave
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Base de dados:
MEDLINE
Assunto principal:
Neoplasias Bucais
/
Carcinoma de Células Escamosas
Idioma:
En
Ano de publicação:
2021
Tipo de documento:
Article