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A NOVEL AND RAPID PREDICTION ASSAY FOR THE EFFECTIVENESS OF IL-6 RECEPTOR SPECIFIC ANTISENSE OLIGONUCLEOTIDES BY PROLIFERATION INHIBITION OF AN INTERLEUKIN-6 DEPENDENT CELL LINE

✍ Scribed by Valeria Lia Varga; Andras Falus; Eva Pallinger; István Novák; Kristóf A. Fülöp; Sara Toth; Stefan Rose-John


Publisher
Elsevier Science
Year
2001
Tongue
English
Weight
123 KB
Volume
25
Category
Article
ISSN
1065-6995

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✦ Synopsis


Interleukin-6 (IL-6) belongs to a family of cytokines that use receptors consisting of a common signal-transducing chain (gp130). Baf/3 cells transfected with the human IL-6 receptor (IL-6R) and gp130 (Baf/3-gp130/IL-6R) can only grow in medium containing IL-6. We attempted to interrupt the signal transducing pathway of IL-6 with the help of antisense oligonucleotides (ASOs) designed against the IL-6R. We used 18 different kinds of antisense oligonucleotides of overlapping sequences around the translational start codon of the human IL-6R. Sense ASOs were used as a control. The proliferation of cells was analysed by H-thymidine incorporation. Cell surface expression of the IL-6R was assessed by FACS analysis. We identified three ASOs which strongly inhibited the proliferation of IL-6 dependent transfected Baf/3 cells. Flow cytometric studies on the suppression of surface expression of IL-6R by ASOs showed a similar pattern. These results should help to clarify the structural requirements of functionally effective ASOs in the inhibition of IL-6R.