H. Shibayama et al., INTERLEUKIN-6 INHIBITS THE CHEMOTAXIS OF HUMAN-MALIGNANT PLASMA-CELL LINES, British Journal of Haematology, 93(3), 1996, pp. 534-541
The chemotaxis of human malignant plasma cells is promoted by two extr
acellular matrix proteins (ECMs): fibronectin (FN) and laminin (LN). W
e examined the effect of the supernatant from a bone marrow stroma cel
l line, KM-101, on the chemotaxis of human malignant plasma cell lines
to assess the chemotaxis-regulatory roles of the bone marrow microenv
ironment. Five human malignant plasma cell lines. FR4ds, OPM4ds, U266/
B1, RPM1-8226 and ARH-77 showed different profiles of the expression o
f beta 1 integrins of FN and LN receptors. FR4ds, OPM4ds, U255/B1, RPM
1-8226 and ARH-77 showed different profiles of the expression of beta
1 integrins of FN and LN receptors. FR4ds, OPM4ds and U266/B1 cells sh
owed chemotaxis promoted by FN (Ch(FN)) and LN (Ch(LN)). ARH-77 cells
showed Ch(FN) or 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 pro
moted by PN or LN. Among the cytokines produced by KM-101 cells, it wa
s postulated that IL-6 mediated this inhibitory effect because anti-IL
-6 monoclonal antibody (MoAb) and anti-IL-6 receptor MoAb significantl
y reversed the inhibition. Recombinant IL-6 (rIL-6) also exhibited a s
imilar inhibitory effect. Because anti-gp130 MoAb significantly revers
ed the chemotaxis inhibitory effect of m-h, the inhibitory signal is p
robably transduced via the signal transducing receptor component, gp13
0, The chemotaxis-regulatory effect is another previously unrecognized
function of tills pleiotropic cytokine, IL-6. High levels of IL-6 in
the bone marrow microenvironment of patients multiple myeloma appears
to be favourable for localization of myeloma cells there.