IFN-gamma production from human Th1 cells is controlled by Raf kinase.
Raf kinase is an important intracellular mediator in T cell signalling and may be crucial for the proliferation of this inflammatory cell. In order to elucidate its effect on cytokine production by human T cells in response to T cell receptor activation, experiments were carried out on human T cell clones using antisense (AS) oligodeoxynucleotides (ODN) to inhibit the expression of Raf kinase. AS ODN to Raf were shown to have a significant effect on a human Th1-like T cell clone, inhibiting antiCD3-induced IFN-gamma secretion by 76%, whereas no inhibitory effect was observed on IL-5 or IL-4 production by a Th2-like clone. IL-2 secretion from both clones was also not affected by the Raf AS ODN. In all cases, a reduction in Raf kinase within the cell was demonstrated by Western blot. Our results clearly demonstrate the importance of Raf kinase in the production of IFN-gamma from Th1 cells, but also show the lack of effect of this intracellular mediator on cytokine (IL-5, IL-4) release from Th2 cells.
Webber
S
S
Department of Pharmacology, Rhône-Poulenc Rorer Ltd., Dagenham Research Centre, UK.
Zheng
R
R
Kamal
A
A
Withnall
M
M
Karlsson
J A
JA
D006801:Humans; D007371:Interferon-gamma / Q000096:biosynthesis*; D007375:Interleukin-1 / Q000096:biosynthesis; D015847:Interleukin-4 / Q000096:biosynthesis; D015848:Interleukin-5 / Q000096:biosynthesis; D016376:Oligonucleotides, Antisense / Q000494:pharmacology; D017346:Protein Serine-Threonine Kinases / Q000502:physiology*; D011518:Proto-Oncogene Proteins / Q000502:physiology*; D019908:Proto-Oncogene Proteins c-raf; D018417:Th1 Cells / Q000378:metabolism*; D014409:Tumor Necrosis Factor-alpha / Q000096:biosynthesis
D007375:Interleukin-1; D015848:Interleukin-5; D016376:Oligonucleotides, Antisense; D011518:Proto-Oncogene Proteins; D014409:Tumor Necrosis Factor-alpha; D015847:Interleukin-4; D007371:Interferon-gamma; D017346:Protein Serine-Threonine Kinases; D019908:Proto-Oncogene Proteins c-raf