Roles of protein phosphatase 1 and 2A in an IL-6-mediated autocrine growth loop of human myeloma cells

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Title
Roles of protein phosphatase 1 and 2A in an IL-6-mediated autocrine growth loop of human myeloma cells
Author(s)
Hyung Sik Kang; Bok Soo Lee; Young Yang; Chong Won Park; Hyun Jung Ha; Kwang Ho Pyun; In Pyo Choi
Bibliographic Citation
Cellular Immunology, vol. 168, no. 2, pp. 174-183
Publication Year
1996
Abstract
Deregulation of IL-6 production is one of the major causes for human multiple myeloma. Exogenous IL-6 stimulated the proliferation of fresh human myeloma cells and the myeloma cell line, U266, which produced IL-6 spontaneously. Anti-IL-6 antibody and IL-6 antisense oligonucleotide suppressed the IL-8-stimulated myeloma cell proliferation, indicating that IL-6 induced the myeloma cell proliferation via an autocrine loop. Okadaic acid, an inhibitor of protein phosphatase 1 and 2A, inhibited the U266 cell proliferation at a concentration of less than 1 ng/ml. At this concentration, okadaic acid suppressed the IL-6-induced IL-6 gene expression of myeloma cells. It seems that the okadaic acid blocked the myeloma cell proliferation by reducing IL-6 synthesis in myeloma cells. In addition, IL-6 itself also regulated IL-6 receptor expression. Analysis by FACScan and RT-PCR showed that anti-PL-6 antibody treatment up-regulated IL-6 receptor expression. Interestingly, the presence of okadaic acid induced the up-regulation of IL-6 receptor expression as well as the down-regulation of IL-6-induced gp130 phosphorylation in the myeloma cells. Taken together, these data suggest that protein phosphatase 1 and 2A are involved in IL-6-mediated autocrine growth of human myeloma cells by modulating IL-6 signaling and IL-6 receptor expression in myeloma cells.
ISSN
0008-8749
Publisher
Elsevier
DOI
http://dx.doi.org/10.1006/cimm.1996.0064
Type
Article
Appears in Collections:
Division of Biomedical Research > Immunotherapy Research Center > 1. Journal Articles
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