TY - JOUR
T1 - Effect of glucocorticoids on the biologic activities of myeloma cells
T2 - Inhibition of interleukin-1β osteoclast activating factor-induced bone resorption
AU - Ishikawa, H.
AU - Tanaka, H.
AU - Iwato, K.
AU - Tanabe, O.
AU - Asaoku, H.
AU - Nobuyoshi, M.
AU - Yamamoto, I.
AU - Kawano, M.
AU - Kuramoto, A.
PY - 1990
Y1 - 1990
N2 - Regulatory effects of glucocorticoids (dexamethasone) on myeloma cells as well as bone resorption in multiple myeloma were investigated. Glucocorticoids significantly inhibited proliferation of myeloma cells, and decreased the messenger RNA (mRNA) expressions of interleukin-6 (IL-6) and secretory type immunoglobulin G (IgG). The inhibitory effects of glucocorticoids on myeloma cell proliferation could be due to the decreased expression of IL-6 mRNA, decreased IL-6 production, and thus suppression of autocrine growth by IL-6, which is an autocrine growth factor for myeloma cells as reported previously (Nature 332:83, 1988). Glucocorticoids also inhibited M-protein secretion by decreasing the levels of secretory type Ig mRNA. On the other hand, because IL-1β rather than lymphotoxin is considered to be a major osteoclast activating factor (OAF) produced by myeloma cells, and glucocorticoids decreased the expression of IL-1β mRNA and markedly suppressed the bone resorbing activity induced by IL-1β OAF in 45Ca-release bone resorption assay, it is suggestive that glucocorticoids could inhibit bone resorption induced by IL-1β OAF in multiple myeloma. Therefore, from these data it is concluded that glucocorticoids could be more effective chemotherapeutic agents in multiple myeloma than we expected, especially with regards to the inhibitory effects on proliferation and M-protein secretion from myeloma cells, as well as bone resorption by myeloma cells.
AB - Regulatory effects of glucocorticoids (dexamethasone) on myeloma cells as well as bone resorption in multiple myeloma were investigated. Glucocorticoids significantly inhibited proliferation of myeloma cells, and decreased the messenger RNA (mRNA) expressions of interleukin-6 (IL-6) and secretory type immunoglobulin G (IgG). The inhibitory effects of glucocorticoids on myeloma cell proliferation could be due to the decreased expression of IL-6 mRNA, decreased IL-6 production, and thus suppression of autocrine growth by IL-6, which is an autocrine growth factor for myeloma cells as reported previously (Nature 332:83, 1988). Glucocorticoids also inhibited M-protein secretion by decreasing the levels of secretory type Ig mRNA. On the other hand, because IL-1β rather than lymphotoxin is considered to be a major osteoclast activating factor (OAF) produced by myeloma cells, and glucocorticoids decreased the expression of IL-1β mRNA and markedly suppressed the bone resorbing activity induced by IL-1β OAF in 45Ca-release bone resorption assay, it is suggestive that glucocorticoids could inhibit bone resorption induced by IL-1β OAF in multiple myeloma. Therefore, from these data it is concluded that glucocorticoids could be more effective chemotherapeutic agents in multiple myeloma than we expected, especially with regards to the inhibitory effects on proliferation and M-protein secretion from myeloma cells, as well as bone resorption by myeloma cells.
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U2 - 10.1182/blood.v75.3.715.715
DO - 10.1182/blood.v75.3.715.715
M3 - Article
C2 - 2297574
AN - SCOPUS:0025098172
VL - 75
SP - 715
EP - 720
JO - Blood
JF - Blood
SN - 0006-4971
IS - 3
ER -