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

• Published in: Cell biology international Vol. 25; no. 3; pp. 253 - 256
• Main Authors: Lia Varga, Valeria, Falus, Andras, Pallinger, Eva, Novák, István, Fülöp, Kristóf A., Toth, Sara, Rose-John, Stefan
• Format: Journal Article
• Language: English
• Published: Oxford, UK Elsevier Ltd 01-03-2001; Blackwell Publishing Ltd
• Subjects: antisense; Base Sequence; Cell Division - drug effects; Cell Line; Flow Cytometry; Humans; Interleukin-6 - pharmacology; interleukin-6 receptor; Oligonucleotides, Antisense - genetics; Oligonucleotides, Antisense - pharmacology; proliferation; Receptors, Interleukin-6 - biosynthesis; Receptors, Interleukin-6 - deficiency; Receptors, Interleukin-6 - genetics; Receptors, Interleukin-6 - metabolism; Signal Transduction - drug effects; Substrate Specificity; Time Factors; proliferation; interleukin-6 receptor; antisense
• ISSN: 1065-6995; 1095-8355
• DOI: 10.1006/cbir.2000.0599

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.