Diverse patterns of cyclooxygenase‐independent metalloproteinase gene regulation in human monocytes

摘要: BACKGROUND AND PURPOSE Matrix metalloproteinase (MMP) production from monocyte/macrophages is implicated in matrix remodelling and modulation of inflammation. However, knowledge the patterns mechanisms gene regulation MMPs their endogenous tissue inhibitors (TIMPs) fragmentary. MMP up-regulation may be a target for cyclooxygenase (COX) prostaglandin (PG) receptor inhibition, but extent COX-independent are unclear. EXPERIMENTAL APPROACH We studied mRNA expression selected protein levels human peripheral blood monocytes before after adhesion, upon stimulation with bacterial lipopolysaccharide (LPS), PGE2 or forskolin culturing monocyte colony-stimulating factor on plastic fibronectin up to 7 days. KEY RESULTS Monocyte adherence 2 h transiently up-regulated COX-2, MMP-1, MMP-7 MMP-10 mRNAs, persistently MMP-2, MMP-9, MMP-14 MMP-19 mRNAs. LPS, selectively increased MMP-10, MMP-12 LPS through COX independently COX. Differential dependence inhibition p42/44 p38 mitogen-activated kinases, c-jun N-terminal kinase inhibitor κB kinase2 paralleled diverse by LPS. Differentiation MMP-7, TIMP-2 TIMP-3 COX; accelerated not TIMP up-regulation. CONCLUSIONS IMPLICATIONS Adhesion, maturation lead selective, regulation, which potential selective signalling inhibitors.