Premium
Decreased IL‐12 production and Th1 cell development by acetyl salicylic acid‐mediated inhibition of NF‐κB
Author(s) -
Mazzeo Daniela,
PaninaBordig Paola,
Recalde Helios,
Sinigaglia Francesco,
D'Ambrosio Daniele
Publication year - 1998
Publication title -
european journal of immunology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.272
H-Index - 201
eISSN - 1521-4141
pISSN - 0014-2980
DOI - 10.1002/(sici)1521-4141(199810)28:10<3205::aid-immu3205>3.0.co;2-8
Subject(s) - salicylic acid , biology , nf κb , production (economics) , microbiology and biotechnology , biochemistry , signal transduction , economics , macroeconomics
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 anti‐inflammatory 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.