Biomedical subjects

R B Zurier

Publications and source records attributed to R B Zurier.

At least 55 records · Page 3Linked to original sources

PubMed1989

Suppression of human synovial cell proliferation by dihomo-gamma-linolenic acid.

Prostaglandin E1 (PGE1) and oils enriched in its precursor fatty acids suppress inflammation and joint tissue injury in several animal models. Since synovial cell proliferation is a hallmark of rheumatoid arthritis, we studied the effect of dihomo-gamma-linolenic acid (DGLA), an immediate precursor of PGE1, on the growth of human adherent synovial cells (ASC) in tissue culture. When stimulated by appropriate concentrations of recombinant interleukin-1 beta (rIL-1 beta), ASC proliferate and produce PGE. DGLA-enriched medium suppressed both baseline and rIL-1 beta-stimulated ASC growth fivefold, compared with medium supplemented with arachidonic acid. Indomethacin reduced the effect of the DGLA. Synovial cells incorporated the DGLA, and rIL-1 beta-stimulated cells that were incubated with DGLA exhibited a 14-fold increase in PGE1 (to 25.2 +/- 6.0 ng/ml, mean +/- SD) and a 70% decrease in PGE2 (to 25.2 +/- 4.2 ng/ml) compared with cells in control medium. At equivalent concentrations (5 x 10(-7) M), PGE1 increased the level of cellular cAMP to a greater extent than did PGE2 (16.8 +/- 2.0 pmoles versus 4.3 +/- 1.9 pmoles, mean +/- SEM). Exogenous PGE1 was also a more effective inhibitor of cell growth. Similarly, cAMP concentrations in cells exposed to DGLA for 6 hours were greater than concentrations in arachidonic acid-enriched cultures (17.8 +/- 3.3 pmoles versus 2.1 +/- 2.0 pmoles). These observations suggest that DGLA can restrain ASC growth, an effect which may be due to its capacity to increase PGE1 production and subsequent cellular cAMP concentration.

8,11,14-Eicosatrienoic Acid↗

PubMed1989

Suppression of acute and chronic inflammation by dietary gamma linolenic acid.

We examined the effect of diets enriched in gamma linolenic acid (GLA) on acute inflammation induced by monosodium urate crystals, and on subacute and chronic inflammation induced by complete Freund's adjuvant in the rat subcutaneous air pouch and in rats with adjuvant induced arthritis. Diets were enriched (15% fat) with borage seed oil (23% GLA) or safflower oil (less than 1% GLA). Diets enriched with GLA suppressed inflammation markedly in all models, whereas the safflower oil diet did not influence the inflammatory response. The degree of inflammation was quantified by measuring pouch exudate cell concentration, lysosomal enzyme activity, volume, protein concentration and prostaglandin E2 and leukotriene B4 concentrations. In the chronic air pouch model, the pouch lining was thickened, invaded by mononuclear cells and exhibited proliferation of lining cells 14 days after adjuvant injection. The lesion was far less severe and usual pouch lining architecture was maintained in animals given dietary GLA. Livers of rats fed borage seed oil were enriched in GLA and dihomo gamma linolenic acid (DGLA), and the DGLA/arachidonate ratio was increased 5-fold compared with animals fed safflower oil. Enrichment of diet with plant seed oils rich in GLA may provide a way to alter generation of prostaglandins and leukotrienes and to influence acute and chronic inflammatory responses.

Acute-Phase Reaction↗

PubMed1988

Suppression of monosodium urate crystal-induced acute inflammation by diets enriched with gamma-linolenic acid and eicosapentaenoic acid.

A subcutaneous air pouch formed in Sprague-Dawley rats was used to study the effect of diets enriched in gamma-linolenic acid (GLA) (in plant seed oil) and eicosapentaenoic acid (EPA) (in fish oil) on acute inflammation induced by monosodium urate crystals. The GLA-enriched diet suppressed significantly the cellular phase of inflammation (polymorphonuclear leukocyte accumulation, crystal phagocytosis, and lysosomal enzyme activity), but it had little effect on the fluid phase (exudate volume and protein concentration). In contrast, the EPA-enriched diet suppressed the fluid phase but not the cellular phase of inflammation. The findings indicate that the fluid and cellular phases of acute inflammation can be controlled independently. A combined diet of fish oil and plant seed oil (EPA-enriched and GLA-enriched) reduced both the cellular and fluid phases of inflammation. Thus, dietary provision of alternative substrates for oxidative metabolism (other than arachidonic acid) modifies monosodium urate crystal-induced acute inflammation.

Animals↗

PubMed1988

Vasoactive intestinal peptide synergistically stimulates DNA synthesis in mouse 3T3 cells: role of cAMP, Ca2+, and protein kinase C.

Vasoactive intestinal peptide synergistically stimulated initiation of DNA synthesis in Swiss 3T3 cells. The peptide stimulated [3H]thymidine incorporation in the presence of insulin and either forskolin or an inhibitor of cAMP phosphodiesterase in a concentration-dependent manner. Half-maximal effect was obtained at 1 nM. At mitogenic concentrations, VIP stimulated a marked accumulation (eightfold) of cAMP. In contrast to other growth-promoting neuropeptides, VIP did not induce an increase in cytosolic free Ca2+ or an activation of protein kinase C. We conclude that neuropeptides can modulate long-term cell proliferation through multiple signaling pathways.

Animals↗

PubMed1988

Synthesis of prostaglandin E by peritoneal macrophages from NZB/W mice.

Peritoneal macrophages from NZB/W (murine lupus) mice spontaneously produce less prostaglandin E (PGE) than peritoneal macrophages from immunologically normal mice. Reduced PGE synthesis is seen as early as 2 months of age and becomes more profound as disease progresses. It is suggested that impaired production of PGE by peritoneal macrophages from NZB/W mice may account in part for abnormal macrophage function observed in these animals.

Age Factors↗

PubMed1988

Suppression of acute inflammation by 15 methyl prostaglandin E1.

Prostaglandins are important regulators of inflammatory responses. The rat subcutaneous air pouch, a model for synovial inflammation, was used to study the effect of systemic injections of prostaglandin E1 (PGE1) and its stable analog 15S,15 methyl prostaglandin E1 (15M PGE1) on nonimmunologically induced acute inflammation. The 15M PGE1 analog was a more effective longer-lasting antiinflammatory agent. Acute inflammatory responses were induced with three diverse stimuli including monosodium urate crystals, leukotriene B4 and formylmethionylleucyl-phenylalanine. Animals were treated with 15 M PGE1 for 2 days before induction of inflammation. Analysis of pouch fluid 6 hours after injection of the inflammatory stimulus indicates that 15M PGE1 treatment suppressed exudate volume and protein concentration, polymorphonuclear leucocyte accumulation and activity of the lysosomal enzyme beta-galactosidase. Treatment with 15M PGE1 was least effective in preventing the fluid phase of inflammation (exudate volume and protein concentration) when leukotriene B4 was used to induce inflammation. Direct observation (dissecting microscope) of pouch lining vessels indicated that 15M PGE1 reduced markedly the intense vascular reactivity (increased number of dilated vessels and filamentous, corkscrew-shaped vessels) usually seen in an acute inflammatory response. The antiinflammatory effect of 15M PGE1 was also documented by histopathology of pouch lining tissue. Treatment with 15M PGE1 reduced substantially the invasion of pouch tissue by polymorphonuclear leucocytes which was induced by all three stimuli of inflammation. Results of these experiments show that systemic administration of 15M PGE1 is capable of suppressing acute inflammation induced by monosodium urate crystals, by the potent soluble naturally occurring mediator of inflammation leukotriene B4, and by the synthetic chemotactic peptide, formylmethionylleucylphenylalanine.

Acute Disease↗

PubMed1988

Relapse of systemic lupus erythematosus in a patient receiving cyclosporine A.

Cyclosporine A (CyA) is being increasingly used as an immunosuppressive agent to treat various autoimmune diseases. A patient with systemic lupus erythematosus (SLE) receiving CyA after renal transplantation suffered a disease relapse associated with high serum CyA levels. Lowering of the CyA dose and the start of steroids resulted in a rapid improvement in her condition. Trials evaluating CyA for SLE should proceed with caution since under certain circumstances this drug may exacerbate disease activity.

Adult↗

PubMed1987

Alteration of uptake and distribution of eicosanoid precursor fatty acids by aspirin.

Aspirin is an important drug in the treatment of numerous disorders, especially rheumatic diseases. Its several mechanisms of action include inhibition of prostaglandin production by acetylation of prostaglandin synthetase. To explore further the modulatory effect of aspirin on eicosanoid production, we examined its effect on uptake and incorporation of fatty acids into phospholipids of human peripheral blood monocytes. Aspirin ingestion by normal volunteers inhibited uptake of arachidonic acid and linoleic acid in monocytes cultured for 3 days. Similar inhibition was observed when cultured normal human peritoneal macrophages were treated with aspirin for 3 days. In contrast, monocytes cultured for 12 days from both normal volunteers who had ingested aspirin and normal cells treated with aspirin in vitro for the first 3 days of a 12-day culture period expressed an increased uptake of both arachidonic and linoleic acids. Similarly, incorporation of fatty acid into phosphatidylcholine was depressed in 3-day cultured cells but was increased in 12-day cultured cells. Thus, aspirin, whether administered in vivo or added in vitro, modulates cellular uptake and incorporation of eicosanoid precursor fatty acids and their insertion into membrane phospholipids in cultured human monocytes and macrophages.

Arachidonic Acid↗

PubMed1987

Prostaglandin E1 inhibits effector T cell induction and tissue damage in experimental murine interstitial nephritis.

Immunosuppressive effects of E-series prostaglandins have been demonstrated in many in vitro assays of immune responsiveness as well as in autoimmune diseases. To explore the mechanisms underlying prostaglandin E1 (PGE1)-associated immunosuppression in autoimmunity, we treated SJL mice immunized to produce immune-mediated interstitial nephritis with PGE1, PGF2 alpha, or vehicle alone. Mice receiving PGE1 treatment do not develop interstitial nephritis, nor do they display delayed-type hypersensitivity (DTH) to the immunizing renal tubular antigen preparation. The observed immunosuppression is critically dependent on PGE1 administration during the period of effector T cell induction. We therefore investigated the effect of PGE1 on the in vitro induction of DTH effector T cells reactive to renal tubular antigens (SRTA). PGE1 inhibits effector T cell induction in a dose-dependent, reversible manner, but has no inhibitory effect on fully differentiated DTH effector cells or SRTA-reactive cell lines. The PGE1 effect is indirect and mediated via nonspecific suppressor lymphokines. This suppression can be overcome by recombinant interleukin 1 (IL-1), which suggests a mechanism related to either diminished IL-1 secretion or target cell sensitivity to IL-1.

Alprostadil↗

PubMed1986

Enhanced phospholipase activity in peripheral blood monocytes from patients with rheumatoid arthritis.

Peripheral blood monocytes (PBM) from patients with rheumatoid arthritis (RA) produce greater amounts of prostaglandins (PG) than do control cells. To further explore the reasons for the increased PG production, we assessed the phospholipase activities in these cells. We found that PBM from patients with severe RA expressed greater phospholipase A2 (PLA2) and phospholipase C (PLC) activities than did the control cells. Enhanced PLA2 activities were observed in RA patient cells when phosphatidylcholine (PC) or phosphatidylethanolamine (PE) were used as substrates. Enhanced PLC activities also were seen when PC, PE, and phosphatidylinositol (PI) were used as labeled substrates. Increased PLC activity was observed whether linoleic acid or arachidonic acid was esterified to the 2 position of the phospholipid substrate used. Because all patients with RA were treated with nonsteroidal antiinflammatory drugs, we examined the effects of aspirin ingestion on phospholipase activities. Aspirin had no consistent effect on PLA2 activities but markedly inhibited PLC activities against PC, PI, and PE with arachidonic acid in the R2 position. That aspirin enhanced PLC activities against PC and PI with linoleic acid in the R2 position, suggests that PLC activity may be regulated in part by the R2 fatty acid. Our results indicate that increased phospholipase activities exhibited by PBM from RA patients may help explain the increased PG production by these cells. The increased phospholipase activities in PBM from RA patients do not appear to be due solely to nonsteroidal antiinflammatory drug therapy.

Arthritis, Rheumatoid↗

PubMed1986

Uptake of fatty acids and their mobilization from phospholipids in cultured monocyte-macrophages from rheumatoid arthritis patients.

Prostaglandins (PG) and related eicosanoids which derive from essential fatty acids are important mediators and modulators of inflammation. Macrophages (M phi), which derive from peripheral blood monocytes (PBM), are prominent cells in the synovium of patients with rheumatoid arthritis (RA), and are a major source of synovial PGE2. In addition, fresh and cultured PBM from RA patients produce more PG than normal control cells. When allowed to mature in culture PBM exhibit many characteristics of macrophages (M-M phi). We examined uptake by M-M phi of eicosanoid precursor fatty acids (FA), their incorporation into cellular phospholipid (PL), and mobilization of FA after cell stimulation. Cultured M-M phi from treated and untreated RA patients (RA M-M phi) took up significantly more linoleic acid (LA), dihomogammalinolenic acid (DHLA) and arachidonic acid (AA) than M-M phi from normal volunteers (N M-M phi). The enhanced uptake of FA observed in 12-day cultures of RA M-M phi was similar to uptake seen in normal human peritoneal macrophages (PM phi). After uptake FA were incorporated mainly into phosphatidylcholine (PC). M-M phi from untreated RA patients incorporated a smaller proportion of [14C]LA into PC (37.0 +/- 12.7% of total PL label) than normal cells (86.0 +/- 4.2%), and a greater proportion of [3H]AA into PC (57.1 +/- 7.1%) than normals (23.9 +/- 6.9%). Stimulation of M-M phi with calcium ionophore A23187 resulted in significantly greater hydrolysis of LA and AA from PC in RA M-M phi from both treated and untreated patients than from PC in N M-M phi. The data indicate that M-M phi from RA patients mature more rapidly in vitro than M-M phi from controls as uptake of FA by RA M-M phi increases with duration of culture and by 12 days in culture equals uptake by normal human peritoneal M phi. Also, RA M-M phi exhibit differences from N M-M phi in uptake, PL distribution, and hydrolysis of eicosanoid precursor FA. Such changes in FA metabolism might influence cell function and inflammatory responses.

8,11,14-Eicosatrienoic Acid↗

PubMed1986

Separation and quantification of prostaglandins E1 and E2 as their panacyl derivatives using reverse phase high pressure liquid chromatography.

Separation and quantification of prostaglandin E1 (PGE1) and prostaglandin E2 (PGE2) were achieved using reverse phase high performance liquid chromatography (HPLC). Panacyl bromide (p-(9-anthroyloxy)phenacyl bromide) (PAB) derivatives of PGE2 and PGE1 were prepared. Reverse phase HPLC using a linear gradient of 56% to 80% acetonitrile in water containing 0.10% acetic acid gave baseline resolution of the two derivatives. A 3 um diameter particle, C18 column provided good resolution and reproducible recoveries. Human synovial tissue cells were incubated with the precursor fatty acids for PGE1 or PGE2 and stimulated with a crude Interleukin 1 (IL-1) preparation. Cells grown in the presence of dihomogammalinolenic acid (DGLA), the precursor for PGE1, made significantly more PGE1 than cells grown in control medium or in the presence of arachidonic acid, precursor for PGE2. PGE2 synthesis was reduced when DGLA was added to cells (resting or IL-1-stimulated).

Acetophenones↗

PubMed1986

Lymphocyte adherence in multiple sclerosis: role of the cytoskeleton and prostaglandin E.

Human peripheral blood lymphocytes from patients with multiple sclerosis (MS) form significantly greater numbers of rosettes with virus infected cells than healthy controls. Because increased lymphocyte adherence in MS may be important to the disease process, we have investigated the mechanisms governing lymphocyte adherence in healthy control volunteers. We have previously shown that prostaglandins E1, E2 (PGE2), and dibutyryl cyclic AMP (db cAMP) and colchicine increase control lymphocyte adherence in healthy control volunteers. Colchicine treatment enhances PGE synthesis in control cells. We now report that colchicine (10(-5) + 10(-7) M) treatment of mononuclear cells does not enhance PGE synthesis in cells from patients with multiple sclerosis. Colchicine treatment did not affect MS lymphocyte adherence.

Aspirin↗

PubMed1985

Monocyte inhibition of lung fibroblast growth: relationship to fibroblast prostaglandin production and density-defined monocyte subpopulations.

Mononuclear cell fibroblast interactions in the normal human lung are poorly understood. Mononuclear cells can regulate fibroblast function and blood monocytes are known to migrate to the lung and participate in pulmonary inflammation. Thus, to clarify mononuclear cell-fibroblast interactions in the normal lung, we obtained supernatants from adherent monocytes and characterized their effect on the log phase growth of human lung fibroblasts. Monocyte supernatants inhibited fibroblast growth in a dose-dependent fashion. The inhibition was the result of an approximately 16,000 MW soluble factor(s) that was heat stable, trypsin sensitive, and chymotrypsin resistant. Elaboration of the factor(s) required monocyte protein synthesis and was not restricted to a density-defined monocyte subpopulation. The inhibitory capacity of a monocyte supernatant was directly related to its ability to stimulate fibroblast prostaglandin production. Blocking fibroblast prostaglandin production reversed the inhibition of fibroblast growth caused by monocyte supernatants. Thus, monocyte inhibition of fibroblast growth may be mediated by fibroblast prostaglandin production. Recruitment of monocytes to the lung and subsequent monocyte inhibition of fibroblast growth may be important in regulating pulmonary fibrosis.

Cell Division↗

PubMed1985

Enhanced phospholipase A2 and C activities of peripheral blood polymorphonuclear leukocytes from patients with rheumatoid arthritis.

Increased concentrations of eicosanoids are found in synovial fluids (SF) from patients with rheumatoid arthritis (RA). SF polymorphonuclear leukocytes (PMN), which derive from peripheral blood, usually account for approximately 90% of the cells in RA SF. Since eicosanoid precursor fatty acids (FA) are liberated by phospholipases from membrane phospholipids, we examined phospholipase A2 and C activities in peripheral blood PMN from patients with RA. Peripheral blood PMN from patients with RA (RA-PMN) exhibit greater phospholipase A2 activities against phosphatidylcholine (PC) and phosphatidylethanolamine (PE), and greater phospholipase C activities against PC, PE, and phosphatidylinositol (PI) than PMN obtained from normal volunteers (N-PMN).

Arthritis, Rheumatoid↗

PubMed1985

Stimulus-dependent inhibition of superoxide generation by prostaglandins.

Infiltrating phagocytes generate superoxide anion (O2-) and prostaglandin (PG) at sites of inflammation. Thus PG-O2- interactions may be important to the initiation and control of inflammation. PGE1, PGE2, and PGD2 inhibit O2- generation (as measured by superoxide dismutase-inhibitable reduction of ferricytochrome c) in a dose-dependent manner (10(-6)-10(-9) M) when human peripheral blood polymorphonuclear leucocytes (PMN) are stimulated with 10(-7) M of the chemotactic peptide, N-formyl-methionyl-leucyl-phenylalanine (FMLP). These PG did not alter O2- generation when PMN were stimulated with 0.1 microgram/ml phorbol myristate acetate (PMA) or 1 mg/ml serum-treated zymosan (STZ). Increments of cyclic AMP (cAMP) (peak: fourfold) in PGE1, PGE2, and PGD2 treated PMN stimulated with PMA or STZ (in which O2- was not reduced) were similar to those in PG-treated PMN stimulated with FMLP (in which O2- was reduced markedly). High concentrations of theophylline and dibutyryl cAMP reduced FMLP and STZ stimulated O2- generation but had no effect on PMA stimulation, suggesting that the stimuli induce different sensitivities to the effects of cellular cAMP. PGF2 alpha had little effect on O2- generation or cAMP levels regardless of the stimulus. PGE1 did not inhibit binding of FML(3H)P to PMN and did not scavenge O2- anions. Therefore the effect of PG on O2- production is dependent on the specific stimulator and an increased concentration of cAMP in activated PMN is by itself not sufficient to limit O2- generation induced by all stimuli.

Alprostadil↗

PubMed1985

Cyclic adenosine 3'5' monophosphate stimulates prostaglandin E production by human adherent synovial cells.

Production of prostaglandin E (PGE) by rheumatoid synovium appears important to regulation of the pathologic process in rheumatoid arthritis. Cells derived from human synovium by proteolytic digestion produce large amounts of PGE which in turn can elevate synovial cell cAMP levels and inhibit cell proliferation. Data presented here indicate that cAMP can further increase production of PGE from adherent synovial cells (ASC). PGE production occurs over 12-72 hr and is not due to the ability of cAMP to inhibit cell proliferation. Exposure of cells to cAMP results in increased release of 3H arachidonic acid from precursors but not in activation of the cyclooxygenase enzyme. This phenomenon suggests the presence in adherent synovial cells of a mechanism for amplifying PGE production.

8-Bromo Cyclic Adenosine Monophosphate↗

PubMed1985

Human alveolar macrophage inhibition of lung fibroblast growth. A prostaglandin-dependent process.

The processes controlling fibrosis in the human lung are poorly understood. Mononuclear cells may be important regulators of fibroblast function, and the alveolar macrophage (AM) is the major mononuclear phagocyte of the human lung. To further understand AM-fibroblast interactions in the lung, supernatants from unstimulated and stimulated adherent human AM were obtained and their effect on the log phase growth of human lung fibroblasts was characterized. Alveolar macrophage supernatants inhibited fibroblast growth in a dose-dependent fashion. This inhibition was the result of a heat-stable (56 degrees C, 1 h), nondialyzable (molecular weight cutoff, 12,000 daltons), soluble factor(s), which was preferentially elaborated by smaller and denser macrophage subpopulations. The inhibitory capacity of an AM supernatant was directly related to its capacity to stimulate fibroblast prostaglandin production. Blocking fibroblast prostaglandin production reversed the inhibition of fibroblast growth caused by AM supernatants. Thus, AM inhibition of fibroblast growth may be mediated in part by fibroblast prostaglandin production. Alveolar macrophage inhibition of fibroblast growth may be important in preventing fibrosis in normal persons and/or in inhibiting the fibrotic response seen with pulmonary inflammation.

Biomechanical Phenomena↗