Expression of Several Matrix Metalloproteinase Genes in Human Monocytic Cells

Abstract

Matrix metalloproteinases (MMP) are a family of structurally related endopeptidases that resorb macromolecules of the extracellular matrix (ECM)¹. They are involved in normal tissue remodeling and wound repair as well as in pathological processes such as the irreversible destruction of joints observed in rheumatoid arthritis (RA)². In addition. MMP catalyze the cleavage of the transmembrane form of tumor necrosis factor (TNF)^3,4. Since cells of the monocyte lineage are major producers of TNF in the rheumatoid synovium we analysed the expression of MMP genes in these cells. To examine the transcriptional activity of MMP genes in undifferentiated monocytic cell lines (MonoMac6, U937) and in nature human monocytes isolated from peripheral blood, we developed an assay that is based on reverse transcription (RT) followed by a polymerase chain reaction (PCR). This screening procedure demonstrates that several MMP genes are transcriptionally active in the cells tested after exposure to a variety of stimuli such as phorbol ester, lipopolysaccharide (LPS) and staphylococcal enterotoxin B (SEB). The data were confirmed by quantitative Northern blot analysis. In conclusion, cells of the monocyte lineage produce high mRNA levels of at least six members of the MMP gene family that could participate in joint destruction by resorption of the ECM and secretion of TNF.