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Interleukin‐6 inhibits the chemotaxis of human malignant plasma cell lines
Author(s) -
SHIBAYAMA HIROHIKO,
TAGAWA SHINICHI,
HATTORI HIDEKI,
HARIGAYA KENICHI,
TAGA TETSUYA,
MACHII TAKASHI,
KITANI TERUO
Publication year - 1996
Publication title -
british journal of haematology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.907
H-Index - 186
eISSN - 1365-2141
pISSN - 0007-1048
DOI - 10.1046/j.1365-2141.1996.d01-1691.x
Subject(s) - chemotaxis , fibronectin , stromal cell , cytokine , cell culture , receptor , chemotaxis assay , microbiology and biotechnology , bone marrow , chemistry , glycoprotein 130 , biology , immunology , extracellular matrix , cancer research , interleukin 6 , biochemistry , genetics
The chemotaxis of human malignant plasma cells is promoted by two extracellular matrix proteins (ECMs): fibronectin (FN) and laminin (LN). We examined the effect of the supernatant from a bone marrow stroma cell line, KM‐101, on the chemotaxis of human malignant plasma cell lines to assess the chemotaxis‐regulatory roles of the bone marrow microenvironment. Five human malignant plasma cell lines, FR4ds, OPM‐1ds, U266/B1, RPMI‐8226 and ARH‐77 showed different profiles of the expression of β1 integrins of FN and LN receptors. FR4ds, OPM‐1ds and U266/B1 cells showed chemotaxis promoted by FN (Ch FN ) and LN (Ch LN ). ARH‐77 cells showed Ch FN but not Ch LN . RPMI‐8226 cells did not show either Ch FN or Ch LN . The supernatant from KM‐101 cells inhibited the chemotaxis of each of these cell lines regardless of whether the chemotaxis was promoted by FN or LN. Among the cytokines produced by KM‐101 cells, it was postulated that IL‐6 mediated this inhibitory effect because anti‐IL‐6 monoclonal antibody (MoAb) and anti‐IL‐6 receptor MoAb significantly reversed the inhibition. Recombinant IL‐6 (rIL‐6) also exhibited a similar inhibitory effect. Because anti‐gp130 MoAb significantly reversed the chemotaxis inhibitory effect of rIL‐6, the inhibitory signal is probably transduced via the signal transducing receptor component, gp130. The chemotaxis‐regulatory effect is another previously unrecognized function of this pleiotropic cytokine, IL‐6. High levels of IL‐6 in the bone marrow microenvironment of patients with multiple myeloma appears to be favourable for the localization of myeloma cells there.