Bacterial lipopolysaccharide induces proliferation of IL-6-dependent plasmacytoma cells by MAPK pathway activation.
Mouse plasmacytomas are appropriate models to study the biology of human multiple myeloma (MM). Growth of murine interleukin-6 (IL-6)-dependent hybridoma/plasmacytoma lines can be stimulated by bacterial lipopolysaccharides (LPS). However, the molecular mechanisms of this phenomenon are still not elucidated. In this study the in vitro action of bacterial LPS on the mouse IL-6-dependent B9 hybridoma/plasmacytoma cell line and two IL-6-dependent hybridomas was investigated. The involvement of different signal transduction pathways was established using specific kinase inhibitors in proliferation assays and immunoblotting analysis of the kinase activity. Selective mitogen-activated protein kinase (MAPK) kinase inhibitor PD989059 inhibited both IL-6- and LPS-induced B9 cell proliferation. In contrast, in H187 and H188 cells, PD98059 inhibited only LPS-, but not IL-6-stimulated cell growth. The kinetics of MAPK activation in all cell lines showed that phosphorylation of p42 MAPK (encoded as ERK2) but not of p44 MAPK (ERK1), was considerably increased after treatment with LPS. We found that in H187 and H188 hybridomas IL-6 induced proliferation by a different STAT3-dependent mechanism. This study demonstrates the key role of the MAPK pathway in LPS-stimulated growth of mouse IL-6-dependent plasmacytoma cells. These findings suggest the presence of signaling mechanism in MM cells inducible by bacterial mitogens and possibly mediated by Toll-like receptors (TLR)--evolutionarily conserved molecules playing a central role in the microbial recognition and initiation of the cellular innate immune response.
Iankov
Lanko
L
Department of Microbiology, Preclinical University Center, Medical University, Zdrave 2 str., 1431 Sofia, Bulgaria. ianko@medfac.acad.bg
Atanasova
Ganka
G
Praskova
Maria
M
Kalenderova
Silvia
S
Petrov
Dragomir
D
Mitev
Vanio
V
Mitov
Ivan
I
D000818:Animals; D002455:Cell Division / Q000502:physiology; D006801:Humans; D015850:Interleukin-6 / Q000378:metabolism*; D008070:Lipopolysaccharides / Q000378:metabolism*; D051379:Mice; D019950:Mitogen-Activated Protein Kinase 1 / Q000378:metabolism*; D048052:Mitogen-Activated Protein Kinase 3 / Q000378:metabolism*; D010954:Plasmacytoma / Q000378:metabolism*; D012475:Salmonella / Q000378:metabolism
D015850:Interleukin-6; D008070:Lipopolysaccharides; D019950:Mitogen-Activated Protein Kinase 1; D048052:Mitogen-Activated Protein Kinase 3