Synovial inflammation and hyperplasia induced by gliostatin/platelet-derived endothelial cell growth factor in rabbit knees

Abstract

Neovascularization, proliferation of synovial cells, and mononuclear cell influx and activation are characteristic events observed in synovial joints in the pathohistology of rheumatoid arthritis (RA). The objective of this study was to examine synovial inflammation in rabbit knees induced by intra-articular administration of human gliostatin/platelet-derived endothelial cell growth factor (GLS/PD-ECGF), which shares a high degree of chemical homology with thymidine phosphorylase (dThdPase) and is known to have angiogenic activity. Purified recombinant human gliostatin (rHuGLS) and its mutant protein, which was prepared by site-directed mutagenesis and which lacks dThdPase activity, were administered at various doses to rabbit knee joints. The effects of rHuGLS and the mutant were examined histologically. Intra-articular injection of rHuGLS resulted in the development of diffuse synovitis resembling RA. The mutant protein also brought about the same effect. These findings suggest that human GLS can cause RA-like synovitis in rabbit knee joints via a mechanism other than its dThdPase activity.

CD44-stimulated human B cells express transcripts specifically involved in immunomodulation and inflammation as analyzed by DNA microarrays

“…This cytokine is known for its involvement in cancer and rheumatoid arthritis and has, for instance, been shown to induce inflammation and hyperplasia in synovial cells. 29 In the cluster described by TTT000, the immunomodulating interleukins IL-6 and IL-1␣ (IL1A) were found. IL-6 is secreted upon inflammation and has a wide array of functions both centrally and peripherally.…”

Upregulation of Thymidine Phosphorylase in Chronic Glomerulonephritis and Its Role in Tubulointerstitial Injury

“…TP is known to be identical to platelet-derived endothelial-cell growth factor (PD-ECGF) [10, 11] and gliostatin [12, 13]. Angiogenesis, which is characterized by the growth of new blood vessels from existing ones, occurs in chronic inflammation and during tumor growth.…”

“…Inflammatory cells such as macrophages express TP in inflammatory diseases [13,17,18,19,20], as do infiltrating macrophages in a variety of tumors [8, 12, 21, 22]. Activated macrophages are a major component of chronic inflammation and play a key role in progressive interstitial injury [23, 24].…”

“…Angiogenesis, which is characterized by the growth of new blood vessels from existing ones, occurs in chronic inflammation and during tumor growth. Among the variety of growth factors and cytokines regulating the process of angiogenesis, TP and its degradation product, 2-deoxy- D -ribose, act as endothelial-cell chemoattractants and angiogenesis-inducing factors [8,9,10,11,12,13,14]. …”

Evaluation of the Mean Platelet Volume in Children with Juvenile Idiopathic Arthritis

“…Other platelet-derived proteins also play a role in proinflammatory and joint destructive actions (17). Platelets release diverse types and substantial amounts of secretory molecules, including chemokines, and proinflammatory molecules (15).…”