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Biomedical subjects

J M Dayer

Publications and source records attributed to J M Dayer.

At least 181 records · Page 10Linked to original sources
PubMed1986

Interleukin 1 is present in normal human epidermis.

We investigated the presence of interleukin 1 (IL 1)-like molecules in normal unstimulated human epidermal tissue. Epidermis from 21 healthy individuals that was prepared by two different methods showed prostaglandin E2 (PGE2) and collagenase stimulating activity for human dermal fibroblasts. All epidermal extracts tested were positive for thymocyte comitogenic activity (lymphocyte activating factor; LAF). Removal of the horny layer decreased epidermal IL 1-like activity. In contrast to epidermal tissue, freshly isolated peripheral blood mononuclear cells (PBMC) contained no detectable PGE2 stimulatory activity. They could, however, produce PGE2 stimulatory activity after culture and stimulation with phytohemagglutinin (PHA) and concanavalin A (Con A). Little membranous IL 1-like activity could be detected in epidermal extracts when using a method that has previously rendered membranous IL 1 from murine proteose peptone-elicited peritoneal macrophages. Gel filtration chromatography yielded double peaks at m.w. approximately 30,000 and approximately 17,000 for all three activities. High pressure liquid chromatography (HPLC) analysis identified two species with a m.w. of approximately 17,000, and one approximately 30,000 species nondissociable in detergent, all having superposable PGE2 and collagenase stimulatory as well as LAF activity. These results establish the existence of IL 1-like molecules, together with a possible precursor, in normal human epidermis. The release of these preformed epidermal IL 1 stores might be important in vivo.

Chromatography, Gel↗
PubMed1986

Type IX collagen is a potent inducer of PGE2 and interleukin 1 production by human monocyte macrophages.

Type IX collagen and its collagenous fragments are potent stimulatory agents on human blood mononuclear cells for the production of prostaglandin E2 and interleukin 1/mononuclear cell factor. Type IX collagen is 2-4-fold more potent that type I and II and 1 alpha-, 2 alpha- and 3 alpha-collagens. This property may be important in the destructive process of cartilage in inflammatory diseases.

Cells, Cultured↗
PubMed1986

Intracellular epidermal interleukin 1-like factors in the human epidermoid carcinoma cell line A431.

Normal human epidermal cells produce, in primary culture, activities which stimulate the release of PGE2 and collagenase by dermal fibroblasts; this factor(s) might play an important role in epidermal-dermal interactions. Since these activities were mainly found in the cell lysates with only little being detected in the conditioned media, we investigated further the problem of cell-associated versus released activity in the model of the human epidermoid carcinoma cell line A431. The activities were consistently found in the cell lysate and in the conditioned media only when the cells were leaky. No membrane-associated activities were identified. Purification of the cytosolic activities were identified. Purification of the cytosolic activities yielded two differently charged species both with a MW of approximately 17K. The copurification of PGE2- and collagenase-stimulating activities with thymocyte comitogenic activity suggests a close physiochemical relation to IL-1. The activities described here might therefore correspond to the intracellular counterpart of epidermal IL-1 formerly described as epidermal cell-derived thymocyte activating factor (ETAF) and identified in the conditioned medium of cultured epidermal cells. These observations are of importance when studying the modulation of these activities.

Carcinoma, Squamous Cell↗
PubMed1986

Effect of interferon-gamma and 1 alpha,25-dihydroxyvitamin D3 on superoxide anion, prostaglandins E2, and mononuclear cell factor production by U937 cells.

Both interferon-gamma (IFN-gamma) and 1 alpha,25-dihydroxyvitamin D3 (1 alpha,25(OH)2D3) induce changes in the human monocytic cell line U937 that may reflect cellular differentiation. The effects of recombinant IFN-gamma and 1 alpha,25(OH)2D3 on U937 cells with regard to the release of superoxide anion (O2-), prostaglandin E2 (PGE2), and mononuclear cell factor (MCF) after stimulation with phorbol myristate acetate (PMA) were examined. PMA did not induce O2- production in untreated cells. A 3-day preincubation with IFN-gamma or 1 alpha,25(OH)2D3 resulted in a 5- to 10-fold increase in PMA-stimulated production of O2- as compared to cells preincubated in medium alone. The response was related to IFN-gamma and 1 alpha,25(OH)2D3 concentrations. In contrast, the PMA-induced production of PGE2 and MCF does not require preincubation with either IFN-gamma or 1 alpha,25(OH)2D3. These results suggest that O2- production and cytokine production (i.e., PGE2 and MCF) are modulated by different signals related to maturation processes.

Calcitriol↗
PubMed1986

Human recombinant interleukin 1 stimulates collagenase and prostaglandin E2 production by human synovial cells.

The pathogenesis and progression of rheumatoid arthritis involves the production of biologically active lymphokines and monokines. Of these, interleukin 1 (IL-1) has been somewhat of a controversial molecule because it seems to evoke various biological responses in several different tissues. In these studies we demonstrate that three biological properties of human monocyte-derived IL-1 (T-lymphocyte activation and human synovial cell prostaglandin E2 and collagenase production) co-purify. The complementary DNA for the prominent pI 7 form of human IL-1 was expressed, purified, and tested. Any controversy now appears resolved since homogeneous recombinant human IL-1 stimulates prostaglandin E2 and collagenase from human synovial cells as well as activates T cells in vitro.

Animals↗
PubMed1986

Prostaglandin E2 and collagenase production by fibroblasts and synovial cells is regulated by urine-derived human interleukin 1 and inhibitor(s).

Interleukin 1 (IL-1) possesses multiple biological activities that may be blocked selectively by different inhibitors. Some known inhibitors block the lymphocyte activating factor (LAF/IL-1) but not the mononuclear cell factor (MCF/IL-1) measured by its capacity to stimulate prostaglandin E2 (PGE2) and collagenase production. The presence of IL-1 in vivo may be difficult to detect due to the presence of inhibitor(s) and the level of the inhibitor(s) may vary depending upon pathological conditions. We have found that urine from three patients with monocytic leukemia (M5) contained high levels of inhibitor(s) of MCF/IL-1, whereas urine of normal subjects did not contain significant amounts. Urine from two patients with other blood neoplasic diseases also contained little inhibitory activity. The MCF/IL-1 inhibitor(s), which also acts on human recombinant IL-1 beta, is approximately 25-35 kD, is not retained on concanavalin A-Sepharose column and can be partially destroyed with urea and boiling. At this stage of the purification the fraction containing the MCF/IL-1 inhibitor(s) also inhibits the LAF/IL-1 assay. However, this inhibitor(s) is probably distinct from other inhibitors already described.

Adult↗
PubMed1986

Characterization of cells from human giant cell tumors of bone.

In vitro cell culture techniques were used to identify and characterize the individual cell types present in human giant cell tumors of bone. Three major cell types were identified based on morphologic characteristics, patterns of specific cell surface antigens, presence of receptors for hormones, and cell products. One population consisted of mononuclear cells that expressed monocyte-macrophage markers. These cells lacked receptors for skeletal hormones and did not persist in culture. Distinct from these cells was a population of mononuclear cells that proliferated in culture and most likely represented the neoplastic element of the tumor. These cells phenotypically resembled connective tissue stromal cells, i. e., they did not express macrophage surface antigens and they produced collagens (Types I and III). They also possessed receptors for parathyroid hormone. The final population of tumor cells consisted of multinucleated giant cells. These cells lacked monocyte-macrophage surface antigens and possessed receptors for calcitonin, a phenotypic marker for osteoclasts. These studies illustrate that in vitro cell culture techniques can be employed to identify and characterize the cell populations of tumors of skeletal tissues, and demonstrate the usefulness of these cell culture models for investigating the biology of bone tumors.

Adult↗
PubMed1986

Normal epidermis contains high amounts of natural tissue IL 1 biochemical analysis by HPLC identifies a MW approximately 17 Kd form with a P1 5.7 and a MW approximately 30 Kd form.

Recently, we demonstrated that normal human epidermis contains IL1. The present work analyses further the significance of this observation by comparing the quantities of epidermal IL1 to those of 7 internal organs in normal rat. Epidermal PGE2 stimulating activity was 200 to 900 fold higher than in the internal organs. Similar results were obtained for the collagenase stimulatory activity and the comitogenic effect on thymocytes. Epidermal IL1 activity in membrane preparations was more than 100 times lower than the activity of the cytosol containing supernatant from the epidermal homogenate. Biochemical analysis by HPLC identified a MW approximately 17 Kd form with a pI 5.7 and a MW approximately 30 Kd form. These results 1) confirm the presence of high amounts of preformed IL1 in normal unstimulated epidermis, 2) show that, compared to 7 internal organs, the epidermis contains the highest activity, 3) suggest that epidermal IL1 is mainly situated in the cytosol, 4) identify a MW approximately 17 Kd form with a pI 5.7, as well as a MW approximately 30 Kd form which might represent an IL1 precursor, 5) demonstrate the copurification of PGE2 and collagenase stimulatory and thymocyte comitogenic activity and 6) give a starting reference for the in vivo study of IL1 activity in pathologic situations.

Animals↗
PubMed1985

Cachectin/tumor necrosis factor stimulates collagenase and prostaglandin E2 production by human synovial cells and dermal fibroblasts.

Cachectin/TNF (tumor necrosis factor), an endotoxin-induced murine macrophage hormone implicated in the pathogenesis of cachexia and shock, has been found capable of stimulating collagenase and prostaglandin E2 (PGE2) production by isolated human synovial cells and dermal fibroblasts. This bioactivity associated with cachectin is comparable to that observed with the monokine interleukin 1 (IL-1), previously suggested as the major mediator of proteolysis. The ability of cachectin/TNF to stimulate collagenase and PGE2 production suggests that it may play a role in tissue destruction and remodelling, as these processes occur in inflammatory diseases.

Animals↗
PubMed1985

Cultured human epidermis cells produce cell-associated interleukin 1-like prostaglandin E2- and collagenase-stimulating factors.

In order to identify factors which may regulate the functions of dermal fibroblasts, cell lysates and conditioned media of cultured human epidermal cells were tested on dermal fibroblasts for the stimulation of prostaglandin E2- and collagenase-production. Both prostaglandin E2- and collagenase-stimulating activities appeared during epidermal cell culture: after 2 d they were detected in the cell lysate, and after 4 d of culture they were found also in the conditioned media. Molecular sieving chromatography of epidermal cell lysates led to the detection of two main peaks showing concomitant prostaglandin E2- and collagenase-stimulating activities at Mr approximately equal to 18 000 and Mr approximately equal to 10 000. A single peak of concomitant prostaglandin E2- and collagenase-stimulating activities were seen at Mr approximately equal to 10 000 in the epidermal cell conditioned media. This suggests that the cell-associated concomitant prostaglandin E2- and collagenase-stimulating activities are processed from a common precursor molecule and released. Collagenase-stimulating activity without accompanying prostaglandin E2 was also detected in the range of Mr approximately equal to 30 000-45 000.

Adolescent↗
PubMed1985

Effects of LTB4 and Ca++ ionophore A23187 on the release by human alveolar macrophages of factors controlling fibroblast functions.

Cultured human alveolar macrophages from smokers with lung cancer produced spontaneously variable amounts of factors stimulating fibroblast proliferation and production of prostaglandin E2 and collagenase by fibroblasts. These biological activities belong to molecules similar or identical to interleukin 1. Exogenous leukotriene B4 added to alveolar macrophage cultures increased the production of these factors. The Ca++ ionophore A23187 was found to have similar effects. By the control of monokine production, leukotriene B4 locally released by inflammatory cells may modulate lung fibroblast functions.

Calcimycin↗
PubMed1985

Human lymphocytes induce a differential release of prostaglandin E2 and interleukin 1-like mononuclear cell factor from normal blood monocytes.

Lymphocytes influence the production of both prostaglandin E2 (PGE2) and interleukin 1 (IL 1) by monocytes. We have examined whether these two products are released concomitantly or not under identical culture conditions using monocyte- and lymphocyte-enriched populations obtained on Percoll gradient. IL 1 was measured as mononuclear cell factor (IL 1/MCF). When incubated with concanavalin A, the monocyte-enriched fraction (MF; 80-91% monocytes), but not the lymphocyte-enriched fraction (LF; 95% lymphocytes) produced increasing amounts of PGE2 and MCF. However, when LF cells were added to MF cells in culture, a 40% to 60% decrease of PGE2 secretion was observed whereas the MCF production remained unchanged or increased up to 26-fold. Such a dissociation between IL 1 and PGE2 production by monocytes indicates independent regulation mechanisms in controlling the immune response under the influence of lymphocytes.

Cell Separation↗
PubMed1985

Cultured human alveolar macrophages from smokers with lung cancer: resolution of factors that stimulate fibroblast proliferation, production of collagenase, or prostaglandin E2.

Marked connective tissue remodelling involves both destruction and repair in inflammatory lung diseases. Throughout the remodelling event, it was reasoned that alveolar macrophages may release substances similar to those produced by blood monocyte-macrophages that affect fibroblast functions, ie, the interleukin 1 family of monokines (or cytokines). We have examined human alveolar macrophage cultures obtained after bronchoalveolar lavage of freshly excised lungs from heavy smokers with bronchial carcinoma. Crude culture media contained fibroblast proliferative activity and collagenase- and PGE2- production-stimulating activity. The main peak of these biological activities was located around approximately 18 kilodaltons (kD) on gel filtration chromatography. Resolution of this peak by high performance liquid chromatography showed the presence of three distinct peaks, with quantitative and qualitative differences in biological activities. This suggests the presence of heterogeneous factors.

Cell Division↗
PubMed1985

Mononuclear cell-conditioned medium containing mononuclear cell factor (MCF), homologous with interleukin 1, stimulates collagen and fibronectin synthesis by adherent rheumatoid synovial cells: effects of prostaglandin E2 and indomethacin.

Adherent rheumatoid synovial cells produce and release into supernatant culture medium latent collagenase and PGE2. The levels of collagenase and PGE2 can be increased by a soluble factor present in mononuclear cell-conditioned medium, partially purified by gel-filtration, which has homologies with interleukin 1, and is produced by monocyte/macrophages. The synovial cell cultures produce collagens (procollagens) and fibronectin as well. The factor(s) present in the mononuclear cell conditioned medium which increases medium levels of collagenase PGE2 also stimulates synthesis of total protein as well as types I and III procollagen by the synovial cells. This stimulation by the monocyte factor is augmented in the presence of indomethacin, which blocks endogenous PGE2 production. Medium levels of fibronectin parallel those of procollagen. The addition of exogenous PGE2 abolishes the effect of indomethacin on collagen and fibronectin synthesis. These observations of mononuclear cell-mediated increases in fibronectin synthesis may account for the high levels of fibronectin found by others in rheumatoid synovium and synovial fluids as the increases in collagen synthesis might also explain the fibrosis observed in some rheumatoid joints.

Arthritis, Rheumatoid↗
PubMed1985

Human circulating monocytes internalize 125I-insulin in a similar fashion to rat hepatocytes: relevance to receptor regulation in target and nontarget tissues.

Circulating monocytes bind 125I-insulin in a specific fashion and have been used to analyze the ambient receptor status in humans. When freshly isolated circulating monocytes are incubated with 125I-insulin and examined by electron microscopic autoradiography, approximately 18% of the labeled material is internalized after 15 minutes at 37 degrees C. By 2 hours at 37 degrees C, approximately one half of the 125I-insulin is internalized. Internalization occurs also at 15 degrees C but at a slower rate. Furthermore, the monocytes bind and internalize 125I-insulin in a manner that mirrors that of major target tissues, such as rat hepatocytes. These data suggest that the insulin receptor of the circulating monocyte might be regulated by adsorptive endocytosis in a manner analogous to that of target tissue, such as the liver.

Animals↗
PubMed1985

Production of mononuclear cell factor by mononuclear phagocytes from rheumatoid synovial fluid.

Collagenase-and PGE1-stimulating activities (mononuclear cell factor or MCF) have been found in culture supernatants from synovial fluid macrophages (SF-M phi) of patients wih rheumatoid arthritis. The apparent molecular weight of the MCF activity present in SF-M phi supernatants was between 15-20,000 daltons, which is similar to interleukin I. All the SF-M phi supernatants from patients tested showed the MCF activity. Our study presents evidence for MCF production by monocyte-macrophages at the local site of the lesion.

Adult↗