TGFbeta down-regulates IFN-gamma production in IL-18 treated NK cell line LNK5E6.
Transforming growth factor beta (TGFbeta) is a critical immunosuppressive cytokine that inhibits the cell-mediated immune responses partly via inhibition of immunostimulatory cytokine production from T cells, NK cells, and macrophages. Here we investigated the effect of TGFbeta on NK cell activation induced by interleukin 18 (IL-18) using a murine NK cell line LNK5E6. IL-18 activated LNK5E6 cells to produce antiviral activity against vesicular stomatitis virus (VSV) and TGFbeta inhibited this activation. TGFbeta inhibited interferon-gamma (IFN-gamma) production in LNK5E6 cells treated with IL-18. TGFbeta also suppressed the IL-18 induced mRNA expression of IFN-gamma. Moreover, TGFbeta did not affect the transcriptional activity of IFN-gamma but decreased the half-life of IFN-gamma mRNA induced by IL-18. These results suggest that the destabilization of IFN-gamma mRNA induced by TGFbeta leads to the inhibition of antiviral activity and IFN-gamma production in IL-18 stimulated LNK5E6 cells.
Hayashi
Hidetoshi
H
Department of Molecular Health Sciences, Graduate School of Pharmaceutical Sciences, Nagoya City University, Mizuho, Nagoya 467-8603, Japan. hhayashi@phar.nagoya-cu.ac.jp
Inoue
Yasumichi
Y
Tsutsui
Hiroko
H
Okamura
Haruki
H
Nakanishi
Kenji
K
Onozaki
Kikuo
K
D000818:Animals; D002460:Cell Line; D003602:Cytotoxicity, Immunologic; D015536:Down-Regulation / Q000502:physiology*; D007371:Interferon-gamma / Q000235:genetics / Q000378:metabolism*; D018664:Interleukin-12 / Q000378:metabolism; D020382:Interleukin-18 / Q000378:metabolism*; D007694:Killer Cells, Natural / Q000166:cytology / Q000378:metabolism*; D008213:Lymphocyte Activation; D051379:Mice; D020871:RNA Stability; D011994:Recombinant Proteins / Q000378:metabolism; D014158:Transcription, Genetic; D016212:Transforming Growth Factor beta / Q000378:metabolism*
D020382:Interleukin-18; D011994:Recombinant Proteins; D016212:Transforming Growth Factor beta; D018664:Interleukin-12; D007371:Interferon-gamma