Modulation of interleukin-1 receptor expression by transforming growth factor-beta in cultured rabbit articular chondrocytes: analysis by reverse transcription-polymerase chain reaction.

Interleukin-1 receptor type I (IL-1RI) expression in cultured rabbit articular chondrocytes (RAC) was studied by reverse transcription-polymerase chain reaction (RT-PCR). A cDNA probe specific for the rabbit IL-1RI gene was constructed using primers derived from the sequence data of the human, murine and chick receptors. Transforming growth factor-beta 1 (TGF beta-1) was shown to transiently increase the level of expected 900-bp PCR product at 1 h of incubation and decrease the expression at 48 and 72 h with no effect at 24 h.

Transforming growth factor-beta (TGF-beta) and articular chondrocytes.

Transforming growth factor-beta (TGF-beta) has a dual effect on the proliferation of joint chondrocytes. In medium with a low serum concentration, it inhibits cell growth, while in medium supplemented with 10% fetal calf serum it stimulates cell growth. This stimulation leads to a higher replication rate an a larger number of cells in the G2/M phase of the cell cycle.

Effect of transforming growth factor-beta 1 (TGF-beta 1) on matrix synthesis by monolayer cultures of rabbit articular chondrocytes during the dedifferentiation process.

Since transforming growth factor-beta (TGF-beta) has been shown earlier to induce the chondrocyte phenotype in embryonic rat mesenchymal cells with production of cartilage-specific type II collagen and proteoglycans, it was of interest to determine whether the factor could also influence the differentiation state of articular chondrocytes maintained in monolayer culture. Using rabbit articular chondrocytes (RAC) in primary and passaged cultures, we demonstrate that the loss of the phenotype accompanying the subculture was not significantly influenced by the presence of TGF-beta. The factor exerted an inhibitory effect on collagen synthesis in a 6-day exposure of primary cultures whereas it stimulated that production throughout the subsequent passages.

Interleukin-1 alpha modulates collagen gene expression in cultured synovial cells.

The effects of porcine interleukin-1 (IL-1) alpha on collagen production were studied in cultured human rheumatoid synovial cells. Addition of 0.05-5 ng of IL-1/ml into the cultures resulted in a dose-dependent decreased rate of collagen released into the medium over 24 h.

Interleukin-1 inhibits the synthesis of collagen by fibroblasts.

Human dermal fibroblasts, exposed to human or porcine Interleukin-1, responded by an inhibition of collagen synthesis in a dose dependent manner. Incubation with Il-1 for more than 8 h was required to see an appreciable effect. The phenomenon was not dependent on the presence of serum in the culture medium.

D-penicillamine inhibition of interleukin-1 production: a possible mechanism for its effect on synovial collagen synthesis?

Collagen production was investigated in cultured rabbit synovial fibroblasts exposed in vitro to D-penicillamine (D-Pen). The results show that these cells are rather insensitive to the drug since only a slight increase of the collagen amount secreted was observed for 48-h exposure to concentrations of 200-400 micrograms/ml. However, fibroblasts derived from the synovium of arthritic rabbits proved to be more susceptible to D-Pen, responding by a marked increase of collagen secretion even for concentrations of 50 micrograms/ml.

In vitro production of collagen by synovial fibroblasts from D-penicillamine-treated arthritic rabbits.

In order to get further insight into the mechanism of D-penicillamine action on synovial tissue collagen synthesis, fibroblasts derived from drug-treated arthritic rabbits were cultured and labelled with radioactive proline. No evident correlation was found between the amount of newly synthesized collagen and the previous treatment of animals. In contrast, the prolyl-hydroxylase activity was reduced in cells from rabbits receiving D-penicillamine.

Mononuclear cell-mediated modulation of synovial cell metabolism. I. Collagen synthesis.

Human PHA-stimulated mononuclear cells produce a factor which inhibits synovial cell collagen and non-collagen protein synthesis, whereas it enhances hyaluronic acid (HA) production. Indomethacin (10(-4)-10(-6) M), a cyclo-oxygenase inhibitor, suppresses this effect, suggesting that the mechanism is prostaglandin-mediated. The active material, of apparent molecular weight 12 000-20 000, also displays the properties of the mononuclear cell factor (MCF) previously described by others, since its stimulates collagenase and PGE2 release by the cultured synovial cells.