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ORIGINAL RESEARCH ARTICLE

Negative Regulation of Interleukin-12 Production by a Rapamycin-Sensitive Signaling Pathway: A Brief Communication

Division of Allergy and Immunology, Department of Pediatrics, University of South Florida, All Children’s Hospital, St. Petersburg, Florida 33701

Interleukin-12 (IL-12), an important cytokine in host defense against microbial pathogens, regulates natural killer and T-cell function(s) including the induction of -interferon production. The major cellular sources of IL-12 are monocytes/macrophages. Bacteria, bacterial products, and intracellular parasites are the most efficient inducers of IL-12 production. In the present study we show that a signal transduction pathway sensitive to rapamycin may have an important role in the regulation/suppression of Staphylococcus aureus–induced IL-12 production in vitro. Human peripheral blood mononuclear cells, monocytes, or a human monocytic cell line THP-1 were stimulated with S. aureus Cowan strain 1 (SAC) in the presence or absence of rapamycin and investigated for production of IL-12 protein by enzyme-linked immunosorbent assay and IL-12 p40 mRNA accumulation by RNase protection assay or real-time quantitative polymerase chain reaction. The results show that rapamycin significantly enhances SAC-induced IL-12 p70 protein production and IL-12 p40 mRNA accumulation. Further the results demonstrate that wortmannin enhances SAC-induced IL-12 p40 mRNA accumulation, whereas Ly294002 does not. These data indicate that a rapamycin-sensitive signaling pathway may act as a negative feedback cascade in the regulatory mechanisms of IL-12 production.

Key Words: interleukin 12 • rapamycin • negative regulation • signal transduction

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