Matrix metalloproteinase and cytokine production by bone marrow adherent cells from multiple myeloma patients.
BACKGROUND
Cultures of bone marrow stromal cells derived from the bone marrow of multiple myeloma (MM) patients were shown to exhibit several abnormalities compared with control cultures from healthy subjects. The aim of the study was to examine whether cultures of bone marrow adherent cells, at low passage level, exhibit differences in matrix metalloproteinases (MMPs) and cytokine production compared with cultures from normal donors.


METHODS
MMP production was evaluated by gel zymography and by ELISA in supernatants of serum-free cultures of bone marrow adherent cells derived from 20 MM patients and 23 healthy controls. Spontaneous and lipopolysaccharide (LPS)- or Newcastle disease virus (NDV)-induced cytokine release was assessed in the supernatants of the cultures by the ELISA method.


RESULTS
Both cultures produced MMP-1, -2, -3, and -9 under serum-free conditions; however, the levels of MMP-1 and MMP-2 were significantly higher in cultures derived from MM patients, while MMP-3 was significantly higher in control cultures. The level of MMP-9 was comparable in the cultures derived from MM patients and controls. All cultures produced interleukin (IL)-10 and IL-11 spontaneously, but after LPS or NDV induction the levels of IL-10, IL-11, interferon alpha, and tumor necrosis factor alpha, were significantly higher in the cultures derived from MM patients than in control cultures.


CONCLUSIONS
The results indicate that both the abnormalities in MMP production and the overproduction of cytokines (in the presence of LPS or virus, which mimic inflammatory conditions) may be involved in bone destruction and tumor spread in multiple myeloma.
Zdzisińska
Barbara
B
Department of Virology and Immunology, Maria Curie-Skłodowska University, Akademicka 19, 20-033, Lublin, Poland. kandem@biotop.umcs.lublin.pl
Walter-Croneck
Adam
A
Dmoszyńska
Anna
A
Kandefer-Szerszeń
Martyna
M
D000328:Adult; D001854:Bone Marrow Cells / Q000201:enzymology* / Q000473:pathology; D002448:Cell Adhesion; D002478:Cells, Cultured; D016207:Cytokines / Q000096:biosynthesis*; D005260:Female; D006801:Humans; D007371:Interferon-gamma / Q000096:biosynthesis; D016753:Interleukin-10 / Q000096:biosynthesis; D008297:Male; D020781:Matrix Metalloproteinase 1 / Q000378:metabolism; D020778:Matrix Metalloproteinase 2 / Q000378:metabolism; D019278:Matrix Metalloproteinase 3 / Q000378:metabolism; D020782:Matrix Metalloproteinases / Q000378:metabolism*; D009101:Multiple Myeloma / Q000201:enzymology* / Q000473:pathology; D014409:Tumor Necrosis Factor-alpha / Q000096:biosynthesis
D016207:Cytokines; C508609:IL10 protein, human; D014409:Tumor Necrosis Factor-alpha; D016753:Interleukin-10; D007371:Interferon-gamma; D020782:Matrix Metalloproteinases; D019278:Matrix Metalloproteinase 3; D020778:Matrix Metalloproteinase 2; D020781:Matrix Metalloproteinase 1