Matrix metalloproteinase and cytokine production by bone marrow adherent cells from multiple myeloma patients

Arch Immunol Ther Exp (Warsz). 2006 Jul-Aug;54(4):289-96. doi: 10.1007/s00005-006-0033-z. Epub 2006 Jul 25.

Abstract

Introduction: 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.

Materials and 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.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Bone Marrow Cells / enzymology*
  • Bone Marrow Cells / pathology
  • Cell Adhesion
  • Cells, Cultured
  • Cytokines / biosynthesis*
  • Female
  • Humans
  • Interferon-gamma / biosynthesis
  • Interleukin-10 / biosynthesis
  • Male
  • Matrix Metalloproteinase 1 / metabolism
  • Matrix Metalloproteinase 2 / metabolism
  • Matrix Metalloproteinase 3 / metabolism
  • Matrix Metalloproteinases / metabolism*
  • Multiple Myeloma / enzymology*
  • Multiple Myeloma / pathology
  • Tumor Necrosis Factor-alpha / biosynthesis

Substances

  • Cytokines
  • IL10 protein, human
  • Tumor Necrosis Factor-alpha
  • Interleukin-10
  • Interferon-gamma
  • Matrix Metalloproteinases
  • Matrix Metalloproteinase 3
  • Matrix Metalloproteinase 2
  • Matrix Metalloproteinase 1