Negative regulation of interleukin-12 production by a rapamycin-sensitive signaling pathway: a brief communication.
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 gamma-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.
Uthaisangsook
Suwannee
S
Division of Allergy and Immunology, Department of Pediatrics, University of South Florida, All Children's Hospital, St. Petersburg, Florida 33701, USA.
Day
Noorbibi K
NK
Hitchcock
Remi
R
Lerner
Aaron
A
James-Yarish
Michelle
M
Good
Robert A
RA
Haraguchi
Soichi
S
D000730:Androstadienes / Q000494:pharmacology; D000903:Antibiotics, Antineoplastic / Q000494:pharmacology; D002460:Cell Line; D002867:Chromones / Q000494:pharmacology; D004791:Enzyme Inhibitors / Q000494:pharmacology; D004797:Enzyme-Linked Immunosorbent Assay; D005786:Gene Expression Regulation; D006801:Humans; D018664:Interleukin-12 / Q000096:biosynthesis*; D007963:Leukocytes, Mononuclear / Q000378:metabolism; D009000:Monocytes / Q000378:metabolism; D009025:Morpholines / Q000494:pharmacology; D012333:RNA, Messenger / Q000378:metabolism; D012260:Ribonucleases / Q000378:metabolism; D015398:Signal Transduction; D020123:Sirolimus / Q000494:pharmacology*; D013211:Staphylococcus aureus / Q000378:metabolism; D000077191:Wortmannin
D000730:Androstadienes; D000903:Antibiotics, Antineoplastic; D002867:Chromones; D004791:Enzyme Inhibitors; D009025:Morpholines; D012333:RNA, Messenger; D018664:Interleukin-12; C085911:2-(4-morpholinyl)-8-phenyl-4H-1-benzopyran-4-one; D012260:Ribonucleases; D020123:Sirolimus; D000077191:Wortmannin