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Biomedical subjects

E C Arner

Publications and source records attributed to E C Arner.

42 records · Page 3Linked to original sources
PubMed1989

Effect of interleukin-1-beta and tumor necrosis factor-alpha on cartilage proteoglycan metabolism in vitro.

The activities of recombinant interleukin-1-beta (IL-1) and recombinant tumor necrosis factor-alpha (TNF) on cartilage proteoglycan metabolism were compared in an organ culture system. IL-1, 1 to 100 ng/ml, and TNF, 10 to 1,000 ng/ml, increased proteoglycan degradation. The concentration-response curves were parallel. The timecourse for degradation was similar for the two cytokines during a 6 day incubation. Both cytokines inhibited the synthesis of new proteoglycan as measured by 35S incorporation. The inhibition curves were parallel and concentration-related between 1 and 10 ng/ml for IL-1 and between 10 and 100 ng/ml for TNF. Maximal inhibition was 60% in the presence of IL-1 (10 ng/ml) or TNF (100 ng/ml), and plateaued at higher concentrations. IL-1 was ten fold more potent than TNF in stimulating proteoglycan breakdown and inhibiting proteoglycan synthesis. Degradation in response to TNF, but not to IL-1, could be blocked by a polyclonal antibody to TNF. A polyclonal antibody to IL-1 could block proteoglycan breakdown in response to both cytokines suggesting that TNF may be mediating proteoglycan degradation by inducing the production of interleukin-1.

Animals↗
PubMed1989

In vivo studies on the effects of human recombinant interleukin-1 beta on articular cartilage.

Interleukin-1 (IL-1) is a cytokine produced by a number of connective-tissue and inflammatory cells which has been shown in organ culture to stimulate the breakdown of cartilage proteoglycans and inhibit their synthesis. Intraarticular injection of human recombinant IL-1 beta into the knee joints of rabbits induced a dose-related decrease in cartilage proteoglycan content and increased infiltration of cells into the synovial fluid. Following a single intraarticular injection, the loss of proteoglycan was maximal at 3 days. By 7 days, proteoglycan content began to return toward control levels. IL-1 also resulted in a dose-related decrease in the ability of cartilage to synthesize new proteoglycan as measured by 35S incorporation. These in vivo effects of IL-1 on articular cartilage closely reflect those effects observed in vitro in organ culture and are consistent with the hypothesis that IL-1 may play a role as a mediator of the loss of cartilage in some arthritic diseases.

Animals↗
PubMed1987

Effect of antiinflammatory drugs on human interleukin-1-induced cartilage degradation.

Human monocyte IL-1 stimulated the release of proteoglycans from cartilage in organ culture in a concentration-related manner. This stimulation required protein synthesis as shown by inhibition with cycloheximide. The metal chelator, 1,10-phenanthroline, inhibited breakdown, suggesting the involvement of a metalloproteinase. Various nonsteroidal anti-inflammatory drugs (100 microM), and the corticosteroids, dexamethasone and hydrocortisone (1-10 microM), were not effective in blocking proteoglycan release. Of the disease modifying agents tested, levamisole was ineffective while the antimalarials, chloroquine (100 microM) and hydroxychloroquine (100 microM), inhibited the action of IL-1. The free-radical inhibitor SOD (5000 U/ml but not 1000 U/ml) was effective while catalase (8000 U/ml) was not. The protective effects of SOD and the antimalarials suggest that oxygen reactive species may play a role, while lack of inhibition with NSAIDs and corticosteroids indicate that arachidonic acid metabolites may not be important in this degradative process.

Animals↗
PubMed1975

Modification of red cell membrane structure by cholesterol-rich lipid dispersions. A model for the primary spur cell defect.

Cholesterol-rich membranes are the hallmark of "spur" red cells. Spur cells accumulate cholesterol from cholesterol-rich serum lipoproteins. Previous studies suggested that this added cholesterol is responsible for both the altered morphology and the destruction of spur cells. To examine this process in the absence of other serum factors, cholesterol-lecithin dispersions with varying amounts of unesterified cholesterol (C) relative to phospholipid (P) were prepared, and their influence on normal human red cells was studied. Cholesterol-rich lipid dispersions (C/P mole ration greater 1.0) transferred cholesterol to both red cell membranes and serum lipoproteins, and cholesterol-poor dispersions (C/P mole ration less 1.0) depleted red cells of cholesterol. Changes in membrane cholesterol paralleled changes in membrane surface area, as calculated from osmotic fragility, with a 0.22 percent variation in surface area per 1.0 percent variation in cholesterol content. Cold-induced compression of membrane surface area was increased in cholesterol-poor red cells (C/P equals 0.4), whereas the surface area of cholesterol-rich membranes (C/P equals 1.80) underwent no compression. Although the Na and K permeability of red cells severely depleted of cholesterol was increased, lesser degrees of depletion had no effect, and the permeability of cholesterol-rich cells was normal. However, increasing membrane cholesterol caused a progressive decrease in red cell deformability, as measured by filtration. Cholesterol-poor red cells were spherocytic in appearance and cholesterol-rich cells were broad and flat, indicative of their surface areas. In addition, cholesterol-rich cells had an irregular contour due to folding of the periphery of the cell. This shape abnormality was identical to that of both spur cells after splenectomy and normal red cells incubated in spur serum. Normalization of the C/P of spur serum by added phospholipid prevented the increase in membrane cholesterol and surface area and the transformation of cell shape. These studies establish that the cholesterol content of red cells is dependent on the C/P of their milieu, either lipoproteins or cholesterol-lecithin dispersions. Moreover, the surface area, deformability, and contour of cholesterol-rich red cells are a direct function of their increased membrane C/P. Although cholesterol-rich spur cells are further modified in the circulation of patients with spleens, this abnormality of the membrane lipid bilayer, induced by cholesterol-rich cholesterol-lecithin dispersions, represents the primary spur cell defect.

Anemia, Hemolytic↗