P2 purinergic receptor signaling and interleukin-1 synergistically induce interleukin-6 production in a human oral squamous carcinoma cell line

Research output: Contribution to journalArticlepeer-review

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.

Original languageEnglish
Pages (from-to)80-90
Number of pages11
Journaljournal of oral biosciences
Volume63
Issue number1
DOIs
Publication statusPublished - 2021 Mar

Keywords

  • ATP
  • IL-1
  • IL-6
  • Oral squamous cell carcinoma
  • P2 purinergic receptors

ASJC Scopus subject areas

  • Medicine (miscellaneous)
  • Biochemistry, Genetics and Molecular Biology(all)
  • Dentistry(all)

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