Lymphokine‐mediated suppression of chondrocyte glycosaminoglycan and protein synthesis

Abstract

Spontaneously released and T cell mitogen augmented lymphokine produced by human mononuclear cells has been shown to induce a concentration dependent reversible suppression of chondrocyte glycosaminoglycan and protein synthesis without significantly enhancing chondrocyte catabolic activity. The modulatory factor(s) is of T cell origin and is trypsin, pronase, and heat sensitive. Prostaglandin inhibitors failed to influence factor formation or activity. Although eluting from Sephadex G-100 over a wide range, peak activity had an approximate molecular weight of 53,000 and appeared distinct from recognized forms of lymphotoxin.Mounting evidence, albeit largely circumstantial, has implicated cell mediated immunologic mechanisms in the pathogenesis of human and experimental animal models of articular disease. Thus the predominant mononuclear cell infiltrating synovial membranes and that present in synovial fluids secured from distinct

Persistence of scleroderma‐like phenotype in normal fibroblasts after prolonged exposure to soluble mediators from mononuclear cells

“…1 (January 1986) repeatedly been shown to alter the behavior of fibroblasts in culture. MNC-SN may modulate the growth (11,12) and synthesis of collagen (13)(14)(15) and GAG (16,17) by fibroblasts. Normal as well as PSS fibroblasts have been shown to respond t o these modulatory influences (16).…”

Characterization of growth factors in human cartilage

“…Their structural characteristics indicate that they are probably different from other exogenous human factors known to stimulate chondrocyte growth and function. These exogenous factors include a group of blood-derived polypeptides collectively referred to as somatomedins [1,2,14], a chondrocyte growth factor (CGF) isolated from the human pituitary gland [ 151, a lymphokine which induces a reversible suppression of glycosaminoglycan and protein synthesis by chondrocytes [4], and a factor(s) produced by adherent mononuclear cells that has been demonstrated to stimulate chondrocytes in organ culture to degrade matrix macromolecules [5]. The cartilage-derived growth factors can be distinguished from the somatomedins, CGF, and lymphokine on the basis of their physical characteristics.…”

“…Two polypeptides have been identified in conditioned media from cultures of human blood mononuclear cells. A lymphokine, described by Herman et al [4], induces a concentration-dependent, reversible suppression of chondrocyte glycosaminoglycan (GAG) and protein synthesis. Jasin and Dingle [5] have identified a factor produced by adherent mononuclear cells which induces the degradation of matrix proteolycan and collagen in cartilage explants in organ culture.…”

Histologic assessment of lymphokine‐mediated suppression of chondrocyte glycosaminoglycan synthesis

“…We have recently shown the capacity of culture supernatants derived by mitogen-induced T cell activation to contain a monocyte dependent, serum inhibitable low molecular weight protease capable of inducing articular cartilage proteoglycan degradation (1 1). In addition, mitogen-induced lymphokines have been shown capable, on a concentration-dependent basis, of inhibiting proteoglycan synthesis in chondrocytes maintained in explant cultures as gauged by diminished uptake of radiolabeled sulfate into macroprecipitable molecules (12). It thus appears that such lymphokines may either B Figure 3.…”

“…F-12 medium was selected for use based upon its proficiency in support of chondrocyte survival (14). Its efficacy in supporting lymphokine production has previously been shown (12).…”