SUBSTANCE-P INDUCES THE SECRETION OF GELATINASE-A FROM HUMAN SYNOVIALFIBROBLASTS

We investigated the secretion of the matrix metalloproteinases, inters titial collagenase (matrix metalloproteinase-l), gelatinase A (matrix metalloproteinase-2) and stromelysin-l (matrix metalloproteinase-3) in human synovial fibroblasts after stimulation with the neuropeptide su bstance P. Human synovial fibroblasts were stimulated with substance P or interleukin-1 beta (IL-1 beta). In the cell culture media gelatina se A, interstitial collagenase and stromelysin-l were identified and t heir activities towards different substrates were determined. Substanc e P in synovial fibroblasts induced an increase in the overall matrix metalloproteinase activity towards the dinitrophenyl-labelled peptide by 85%, against an increase of 124% after stimulation with IL-1 beta. In case of substance P stimulation, the increase in activity reflects a significantly enhanced secretion of gelatinase A, whereas no signifi cant increase of stromelysin-l and collagenase secretion could be obse rved. The matrix metalloproteinase pattern showing the highest gelatin ase A secretion was obtained after stimulation with substance P. This pattern was very pronounced and differed very clearly from the pattern seen after IL-1 beta stimulation which caused a significant rise in c ollagenase and stromelysin-l activity. We assume that distinct stimula tion pathways are involved and that the neuropeptide (substance P), wh ich is always present in the inflamed joint, plays its own and separat e role in proliferative processes leading to the cartilage destruction .