[Activation of PKA pathway inhibits reactivity of human myeloma cell line-U266 to IL-6].
OBJECTIVE
To study the effects of PKA pathway activation on the biological function and signal transduction of IL-6 in a human myeloma cell line-U266.


METHODS
The effect of IL-6 on the growth of U266 cells was shown by MTT; electrophoretic mobility shift assay (EMSA) was used to detect the activation of two transcription factors(TFs)-STAT3 and the NF-IL-6 by IL-6, which were involved in the JAK/STAT and Ras/NF-IL-6 signal transduction pathways. Then, the cells were treated with IL-6 and Forskolin (FK), an agonist of the PKA pathway. The changes in the cell growth and activation of the two TFs were exhibited by MTT and EMSA.


RESULTS
(1) IL-6 could promote the proliferation of U266 cells, (2) both JAK/STAT and Ras/NF-IL-6 signal transduction pathways were activated by IL-6 in the U266 cells and (3) Cell proliferation and activation of the two IL-6 signal transduction pathways were inhibited by Forskolin; down-regulating the actiration of these two signal transduction pathways at the same time.


CONCLUSIONS
The inhibition of cell growth, mediated by the activation of the PKA pathway, is related to the down-regulated activation of the two IL-6 signal transduction pathways.
Song
J
J
Institute of Basic Medical Sciences, Academy of Military Medical Sciences, Beijing 100850, China.
Li
Y
Y
Shen
B
B
D022782:CCAAT-Enhancer-Binding Protein-beta / Q000187:drug effects / Q000378:metabolism; D002455:Cell Division / Q000187:drug effects; D005576:Colforsin / Q000494:pharmacology; D017868:Cyclic AMP-Dependent Protein Kinases / Q000378:metabolism*; D004268:DNA-Binding Proteins / Q000187:drug effects / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D004789:Enzyme Activation / Q000187:drug effects; D006801:Humans; D015850:Interleukin-6 / Q000494:pharmacology*; D009101:Multiple Myeloma / Q000378:metabolism* / Q000473:pathology; D050796:STAT3 Transcription Factor; D015398:Signal Transduction / Q000187:drug effects; D015534:Trans-Activators / Q000187:drug effects / Q000378:metabolism; D014407:Tumor Cells, Cultured / Q000187:drug effects
D022782:CCAAT-Enhancer-Binding Protein-beta; D004268:DNA-Binding Proteins; D015850:Interleukin-6; D050796:STAT3 Transcription Factor; C494086:STAT3 protein, human; D015534:Trans-Activators; D005576:Colforsin; D017868:Cyclic AMP-Dependent Protein Kinases