Cyclooxygenase-independent inhibition of dendritic cell maturation by aspirin

R. Matasic, Allan B Dietz, S. Vuk-Pavlovic

Research output: Contribution to journalArticle

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Abstract

When immature human myeloid dendritic cells were differentiated in vitro in the presence of aspirin, they were unable to stimulate T-cell proliferation. Aspirin and its major metabolite salicylate changed the surface marker phenotype of dendritic cells. The drugs particularly suppressed the levels of CD83 and the secreted p40 unit of interleukin-12 (IL-12), both markers of mature dendritic cells; 50% inhibitory concentration (IC50) values were 2.5 mM, a concentration more than 100 times greater than the concentration at mid-point inhibition (ID50) value for inhibition of prostaglandin synthesis. Concomitantly, the levels of CD14, a marker of monocytes/macrophages, increased above the levels found in immature dendritic cells. Cyclooxygenase inhibitors ketoprofen, indomethacin and NS-398 had no effect at concentrations more than a thousand-fold higher than their IC50 values. The effects were independent of the presence of prostaglandin E2 in the medium. Salicylates suppressed activation of the nuclear transcription factor κB, which regulates dendritic cell differentiation, but their effects on mature dendritic cells were negligible. Hence, aspirin inhibits dendritic cell function by inhibiting their terminal differentiation at concentrations achieved in the blood of patients chronically treated with high-dose aspirin.

Original languageEnglish (US)
Pages (from-to)53-60
Number of pages8
JournalImmunology
Volume101
Issue number1
DOIs
StatePublished - 2000

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Prostaglandin-Endoperoxide Synthases
Dendritic Cells
Aspirin
Inhibitory Concentration 50
Salicylates
Ketoprofen
Cyclooxygenase Inhibitors
Myeloid Cells
Interleukin-12
Dinoprostone
Indomethacin
Prostaglandins
Monocytes
Cell Differentiation
Transcription Factors
Macrophages
Cell Proliferation
T-Lymphocytes
Phenotype
Pharmaceutical Preparations

ASJC Scopus subject areas

  • Immunology

Cite this

Cyclooxygenase-independent inhibition of dendritic cell maturation by aspirin. / Matasic, R.; Dietz, Allan B; Vuk-Pavlovic, S.

In: Immunology, Vol. 101, No. 1, 2000, p. 53-60.

Research output: Contribution to journalArticle

Matasic, R. ; Dietz, Allan B ; Vuk-Pavlovic, S. / Cyclooxygenase-independent inhibition of dendritic cell maturation by aspirin. In: Immunology. 2000 ; Vol. 101, No. 1. pp. 53-60.
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