Substance P Induces the Secretion of Gelatinase A from Human Synovial Fibroblasts

Abstract

Summary: We investigated the secretion of the matrix metalloproteinases, interstitial collagenase (matrix metalloproteinase-1), gelatinase A (matrix metalloproteinase-2) and stromelysin-1 (matrix metalloproteinase-3) in human synovial fibroblasts after stimulation with the neuropeptide substance P.Human synovial fibroblasts were stimulated with substance P or interleukin-lß (IL-lß). In the cell culture media gelatinase A, interstitial collagenase and stromelysin-1 were identified and their activities towards different substrates were determined.Substance 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-lß. In case of substance P stimulation, the increase in activity reflects a significantly enhanced secretion of gelatinase A, whereas no significant increase of stromelysin-1 and collagenase secretion could be observed.The matrix metalloproteinase pattern showing the highest gelatinase A secretion was obtained after stimulation with substance P. This pattern was very pronounced and differed very clearly from the pattern seen after IL-lß stimulation which caused a significant rise in collagenase and stromelysin-1 activity. We assume that distinct stimulation pathways are involved and that the neuropeptide (substance P), which is always present in the inflamed joint, plays its own and separate role in proliferative processes leading to the cartilage destruction.Introduction broblasts (5, 11). In these cells, but also in monocytes/

Evidence that exogenous and endogenous fractalkine can induce spinal nociceptive facilitation in rats

“…This activation, in turn, would allow release of the chemokine domain of fractalkine from neurons. Although no studies to date have examined the conditions under which matrix metalloproteinases in spinal cord are activated, it is known that substances critically involved in pain enhancement in the dorsal horns (excitatory amino acids, substance P, nitric oxide, prostaglandin E2) can each activate matrix metalloproteinases in other systems (Hecker‐Kia et al ., 1997; Lyons et al ., 2002; Szklarczyk et al ., 2002; Mayers et al ., 2003). If these substances can also activate matrix metalloproteinases in spinal cord, then their release in response to peripheral inflammation and injury could potentially lead to the activation of matrix metalloproteinases expressed by neurons, astrocytes and/or microglia (Cross & Woodroofe, 1999; Szklarczyk et al ., 2002).…”

Substance P regulates the expression of matrix metalloproteinases and tissue inhibitors of metalloproteinase in cultured human gingival fibroblasts

“…In human synovial fibroblasts, Hecker‐Kia et al . have shown that Substance P stimulation significantly enhanced secretion of MMP‐2, whereas no significant increase of MMP‐1 and ‐3 secretions was observed (35).…”

“…The regulation of TIMP-1 seems to differ from that of the MMPs, particularly in terms of induction by cytokines in gingival fibroblasts (34). In human synovial fibroblasts, Hecker-Kia et al have shown that Substance P stimulation significantly enhanced secretion of MMP-2, whereas no significant increase of MMP-1 and -3 secretions was observed (35).…”

Optimized Fmoc solid‐phase synthesis of Thymosin α1 by side‐chain anchoring onto a PEG resin

“…Inoue et al (2001) suggested that bFGF plays an important role as an inductor or a promoter for the production of substance P in synovial fibroblasts derived from patients with RA and OA. Substance P is known as a potent mediator of inflammation in various tissues because it promotes the secretion of IL‐1 and TNFα in monocytes (Kimball et al, 1988; Lotz et al, 1988); it also stimulates synovial cells to produce prostaglandin E 2 (PGE 2 ), MMPs (Lotz et al, 1987; Hecker‐Kia et al, 1997) and reactive oxygen species (ROS) (Tanabe et al, 1996). However, the biological function(s) of substance P or its receptor in articular chondrocytes is not clear.…”