The plasmacytoma growth inhibitor restrictin-P is an antagonist of interleukin 6 and interleukin 11. Identification as a stroma-derived activin A.
A stromal protein, designated restrictin-P, that specifically kills plasma-like cells was purified to homogeneity and shown to be identical with activin A. The specificity to plasma-like cells stemmed from the ability of restrictin-P/activin A to competitively antagonize the proliferation-inducing effects of interleukin (IL) 6 and IL-11. Restrictin-P further interfered with the IL-6-induced secretion of acute phase proteins by HepG2 human hepatoma cells and with the IL-6-mediated differentiation of M1 myeloblasts. A competition binding assay indicated that restrictin-P did not interfere with the binding of IL-6 to its receptor on plasma-like cells, suggesting that it may act by intervening in the signal transduction pathway of the growth factor. Indeed, concomitant addition of restrictin-P and IL-6 to cytokine-deprived B9 hybridoma cells was followed by sustained overexpression of junB gene until cell death occurred, while IL-6 alone caused a transient increase only. This altered response to IL-6 stimulation was accompanied by a moderate increase in STAT protein activation. Thus, in this study, we identified the plasmacytoma growth inhibitor, restrictin-P, as being activin A of stromal origin. It is shown that activin A is an antagonist of IL-6-induced functions and that it modifies the IL-6 signaling pattern.
D028341:Activins; D000595:Amino Acid Sequence; D000818:Animals; D002455:Cell Division / Q000187:drug effects; D002460:Cell Line; D004268:DNA-Binding Proteins / Q000378:metabolism; D006023:Glycoproteins / Q000494:pharmacology*; D006131:Growth Inhibitors / Q000494:pharmacology*; D006801:Humans; D007265:Inhibins / Q000494:pharmacology*; D036341:Intercellular Signaling Peptides and Proteins; D017370:Interleukin-11 / Q000037:antagonists & inhibitors*; D015850:Interleukin-6 / Q000378:metabolism; D051379:Mice; D008969:Molecular Sequence Data; D050796:STAT3 Transcription Factor; D017154:Stromal Cells / Q000737:chemistry; D015534:Trans-Activators / Q000378:metabolism; D000093242:Interleukin-6 Inhibitors
D028341:Activins; D004268:DNA-Binding Proteins; D006023:Glycoproteins; D006131:Growth Inhibitors; D007265:Inhibins; D036341:Intercellular Signaling Peptides and Proteins; D017370:Interleukin-11; D015850:Interleukin-6; D050796:STAT3 Transcription Factor; D015534:Trans-Activators; D000093242:Interleukin-6 Inhibitors; C494086:STAT3 protein, human; C494087:Stat3 protein, mouse; C069698:restrictin-P