Decreased IL-12 production and Th1 cell development by acetyl salicylic acid-mediated inhibition of NF-κB

Daniela Mazzeo, Paola Panina-Bordignon, Helios Recalde, Francesco Sinigaglia, Daniele D'Ambrosio

Research output: Contribution to journalArticle

50 Citations (Scopus)

Abstract

IL-12 is a 75-kDa heterodimeric cytokine composed of two covalently linked p35 and p40 chains. This pro-inflammatory cytokine plays a prominent role in the development of Th1 cell-mediated immune responses. Th1 cell-mediated immune responses have been implicated in the pathogenesis of chronic inflammatory autoimmune diseases. Thus, IL-12 appears to be a critical factor in the generation and mainteinance of chronic inflammatory conditions. In this study, we investigated the effects of a commonly prescribed antiinflammatory drug, acetyl salicylic acid (ASA), on IL-12 production and Th1 cell development. ASA was found to inhibit secretion of the IL-12 heterodimer as well as p40 monomer by human monocytic cells. This was associated with the down-regulation of IL-12p40 mRNA expression. Analysis of the regulation of the p40 gene promoter revealed that ASA inhibited NF-κB activation and binding to the p40-κB site in the p40 promoter, leading to transcriptional repression of the p40 gene. Addition of ASA to an in vitro T helper cell differentiation system, at concentrations compatible with plasma levels reached during anti-inflammatory therapy, resulted in reduced development of Th1 cells. These results suggest that the inhibition of NF-κB activation by ASA leads to down-regulation of IL-12 production and inhibition of Th1 cell development.

Original languageEnglish
Pages (from-to)3205-3213
Number of pages9
JournalEuropean Journal of Immunology
Volume28
Issue number10
DOIs
Publication statusPublished - Oct 1998

Fingerprint

Th1 Cells
Salicylic Acid
Interleukin-12
Anti-Inflammatory Agents
Down-Regulation
Interleukin-12 Subunit p40
Cytokines
Genes
Autoimmune Diseases
adjuvant P40
Cell Differentiation
Messenger RNA
Pharmaceutical Preparations

Keywords

  • Autoimmunity
  • Cytokine
  • Th1
  • Th2

ASJC Scopus subject areas

  • Immunology

Cite this

Decreased IL-12 production and Th1 cell development by acetyl salicylic acid-mediated inhibition of NF-κB. / Mazzeo, Daniela; Panina-Bordignon, Paola; Recalde, Helios; Sinigaglia, Francesco; D'Ambrosio, Daniele.

In: European Journal of Immunology, Vol. 28, No. 10, 10.1998, p. 3205-3213.

Research output: Contribution to journalArticle

Mazzeo, Daniela ; Panina-Bordignon, Paola ; Recalde, Helios ; Sinigaglia, Francesco ; D'Ambrosio, Daniele. / Decreased IL-12 production and Th1 cell development by acetyl salicylic acid-mediated inhibition of NF-κB. In: European Journal of Immunology. 1998 ; Vol. 28, No. 10. pp. 3205-3213.
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