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Biomedical subjects

F X Maquart

Publications and source records attributed to F X Maquart.

At least 55 records · Page 3Linked to original sources
PubMed1993

Fibroblastic rheumatism: clinical, histological, immunohistological, ultrastructural and biochemical study of a case.

We report a case of fibroblastic rheumatism (FR). Only eight other cases of this recently described entity have been reported previously. FR is characterized by polyarthralgia and joint stiffness without joint destruction, associated with cutaneous nodules and sclerodactyly. Histology shows an increase in the number of fibroblasts and marked dermal fibrosis. Rheumatological and skin manifestations may improve with corticosteroid therapy. In our patient, immunohistochemical studies of involved and uninvolved skin showed an increase in fibronectin and tenascin deposition. In the dermis, the hyperplastic cells had phenotypic features of muscle, suggesting myofibroblastic differentiation. Ultrastructural study showed an increase in active fibroblastic cells with features of myofibroblasts. A hyperproliferative capacity was observed in fibroblasts cultured from involved skin. Biochemical studies of the production of collagen and non-collagen proteins were performed on these cultured cells, and showed a reduction in collagen and non-collagen protein synthesis by FR fibroblasts. Thus, FR appears to differ from other fibrotic skin diseases such as scleroderma, in that dermal fibrosis may be due predominantly to fibroblast proliferation with myofibroblastic differentiation without any increase in collagen synthesis.

Cell Adhesion Molecules, Neuronal↗
PubMed1993

Tubule formation by human surface respiratory epithelial cells cultured in a three-dimensional collagen lattice.

Human surface respiratory epithelial (HSRE) cells from nasal polyps have been cultured within collagen lattices in a serum-free defined medium. Cell growth observed over a period of 12 days showed a population doubling time of 36 h. Under these culture conditions, we observed a contraction of the lattices. Phase-contrast light microscopy and transmission electron microscopy demonstrated that the HSRE cells formed tubular ductlike structures. Lumens formed by HSRE cells were surrounded by cuboidal-shaped polarized cells with numerous ciliated cells, secretory cells, and undifferentiated cells. Epidermal growth factor (EGF) was observed to stimulate the tubule formation and the contraction of the lattices. Videomicroscopic observations and analysis of the ciliary beating frequency (CBF) demonstrated that the cilia were homogeneously distributed on the whole apical surface of the ciliated cells and that their movement was well coordinated, with a CBF similar to that observed in outgrowth cells from cultured human nasal and tracheal epithelia. Immunofluorescent staining of basement membrane components synthesized and secreted by cells revealed the presence of type III collagen around the tubules. Type IV collagen and laminin were present in the cytoplasm and at the periphery of the cells. The biotin-streptavidin-gold immunocytochemical technique with monoclonal anti-mucin antibody showed intracellular localization of mucins in secretory granules of the secretory cells. With the use of substrate gel electrophoresis polyacrylamide gels impregnated with gelatin, collagenase activity was detected in the conditioned medium of the cultured HSRE cells. These results suggest that both three-dimensional collagen gel and soluble factors such as EGF regulate tubule formation by HSRE cells. Moreover, the capacity of the epithelial cells to contract the gel suggests they may be involved in the wound healing process.

Basement Membrane↗
PubMed1993

In vivo stimulation of connective tissue accumulation by the tripeptide-copper complex glycyl-L-histidyl-L-lysine-Cu2+ in rat experimental wounds.

The tripeptide-copper complex glycyl-L-histidyl-L-lysine-Cu2+ (GHK-Cu) was first described as a growth factor for differentiated cells. Recent in vitro data showed that it possesses several properties of a potential activator of wound repair. We investigated the effects of GHK-Cu in vivo, using the wound chamber model described previously (Schilling, J.A., W. Joel, and M.T. Shurley, 1959. Surgery [St. Louis]. 46:702-710). Stainless steel wire mesh cylinders were implanted subcutaneously on the back of rats. The animals were divided into groups that received sequential injections into the wound chamber of either saline (control group) or various concentrations of GHK-Cu. At the end of the experiments, rats were killed, wound chambers were collected, and their content was analyzed for dry weight, total proteins, collagen, DNA, elastin, glycosaminoglycans, and specific mRNAs for collagens and TGF beta. In the GHK-Cu-injected wound chambers, a concentration-dependent increase of dry weight, DNA, total protein, collagen, and glycosaminoglycan contents was found. The stimulation of collagen synthesis was twice that of noncollagen proteins. Type I and type III collagen mRNAs were increased but not TGF beta mRNAs. An increase of the relative amount of dermatan sulfate was also found. A control tripeptide, L-glutamyl-L-histidyl-L-proline, had no significant effect. These results demonstrate that GHK-Cu is able to increase extracellular matrix accumulation in wounds in vivo.

Animals↗
PubMed1993

[Physiopathology of scleroderma].

Scleroderma (systemic sclerosis) is a connective tissue disease characterized by an excessive accumulation of collage in the main body organs. The subsequent progressive fibrosis may result in severe functional impairment of the tissue(s) involved. In this paper, recent advances in the understanding of the disease are reviewed. Particular emphasis is placed on the role played by vascular lesions, inflammatory cell infiltrates, autoimmunity and possibly abnormal secretion of cytokines in the disturbance of connective tissue production. A better knowledge of the pathophysiological process involved in scleroma might lead to the development of new therapeutic approaches.

Antibody Formation↗
PubMed1992

[Synthesis of collagen in culture of endothelial cells of the human umbilical vein. Effects of cyclosporine A].

Interstitial renal fibrosis and gingival hypertrophy are frequent side-effects of cyclosporin A which have been attributed to a dysfunction of extracellular matrix synthesis. Endothelial cells might participate in the matrix accumulation observed. We studied the effects of increasing concentrations of cyclosporin A on protein synthesis by human umbilical vein endothelial cells. Collagen synthesis decreased significantly to 800 ng/ml in both medium and cell layer. The percentage of hydroxylation of its proline residues decreased significantly as from 400 ng/ml. The main proteins, analysed by SDS-PAGE, were thrombospondin, fibronectin and the alpha 1 and alpha 2 chains of type IV collagen. These fractions did not show any change after 24 hours exposure to 200 ng/ml of cyclosporin A. These results demonstrate an inhibitory effect of cyclosporin A on collagen synthesis by human umbilical vein endothelial cells. Consequently, matrix accumulation by increased collagen synthesis in cyclosporin A treated patient may not be directly related to the drug effect on endothelial cells.

Collagen↗
PubMed1992

Interleukin-4 stimulates collagen gene expression in human fibroblast monolayer cultures. Potential role in fibrosis.

A role for the cytokines produced by tissue-infiltrated inflammatory cells (mainly T-lymphocytes and mast cells) in the pathophysiology of fibrosis has been suggested by several groups. Among the products of these cells, interleukin-4 (IL-4) might be one of the factors involved in the initiation of the fibrotic process. We studied the effects of recombinant human IL-4 on human fibroblast monolayer cultures. IL-4 (10 and 100 U/ml) induced a dose-dependent increase of collagen production. Non-collagen protein synthesis was not significantly altered. A concomitant increase of pro-alpha 1(I) collagen mRNAs was observed, showing that IL-4 acts at a pre-translational level.

Blotting, Northern↗
PubMed1992

Different regulation of collagen I gene transcription in three-dimensional lattice cultures.

Human skin fibroblasts were cultivated in confluent monolayers, retracting collagen lattices, retracting fibrin lattices and non-retracting fibrin lattices and the expression of messenger RNA specific for the alpha 1 chain of type I procollagen comparatively studied by Northern blot and dot blot hybridization. Two factors contribute to the lower level of procollagen messenger RNA in collagen lattices: the retraction and the nature of the fibrillar protein that constitutes the lattices. Fibrin lattices, when they do not retract, make as much collagen and procollagen mRNA as monolayer confluent cells.

Blotting, Northern↗
PubMed1992

Insulin-like growth factor-I (IGF-I) stimulates protein synthesis and collagen gene expression in monolayer and lattice cultures of fibroblasts.

Fibroblasts cultivated in three-dimensional tissue-like matrices are characterized by a slowed metabolism and a decrease of protein synthesis, unless they are submitted to physical tensions. We checked the effects of insulin like growth factor-I (IGF-I), known as a potent stimulator of mitogenesis and protein synthesis for many cell types, in various models of cultures: confluent monolayers, collagen lattices, non-retracting or retracting fibrin lattices. IGF-I (1-100 ng.ml-1) had no effect on cell divisions in lattice cultures. It was able to stimulate collagen lattice retraction when the medium was supplemented with low concentrations of serum. IGF-I at 10 or 100 ng.ml-1 stimulated collagen and non-collagen syntheses in all culture systems, but stimulation of collagen synthesis only began at the highest concentration (100 ng.ml-1) in retracted lattices. Northern blot and dot-blot analyses of mRNAs extracted from monolayer cultures of fibroblasts showed that IGF-I stimulated pro alpha 1(I) collagen synthesis at the pretranslational level. Cycloheximide (7.5 micrograms.ml-1) completely inhibited pro alpha 1(I) collagen gene expression induced by IGF-I. These results show that IGF-I is a potent stimulus for protein synthesis and collagen gene expression in monolayers and tridimensional cultures of fibroblasts, but that it exerts no mitogenic activity in tridimensional lattices. Synergistic associations of IGF-I with other growth factors will have to be found in order to reverse the quiescent status of fibroblasts in lattices.

Cell Count↗
PubMed1992

Stimulation of sulfated glycosaminoglycan synthesis by the tripeptide-copper complex glycyl-L-histidyl-L-lysine-Cu2+.

Glycyl-L-histidyl-L-lysine-copper (II) complex (GHK-Cu) is a naturally occurring tripeptide with potential healing properties. We studied the effect of GHK-Cu on the synthesis of glycosaminoglycans (GAGs) by normal human fibroblasts in culture. Cells were incubated with 3H glucosamine and 35S sulfate and the radioactivity of isolated GAGs was determined. GHK-Cu induced a dose-dependent increase of the synthesis of total GAGs secreted into the culture medium and those associated with the cell layer. The effect of GHK-Cu was biphasic with a maximal stimulation at 10(-9) to 10(-8) M. At higher concentrations, the rate of synthesis returned progressively to that of control cultures. Electrophoretic analysis of the different GAG populations showed that GHK-Cu preferentially stimulated the synthesis of extracellular dermatan sulfate and cell layer associated heparan sulfate. No influence of GHK-Cu on the synthesis of hyaluronic acid was observed. GHK-Cu stimulation of GAG synthesis may be one of the phenomenons implicated in the wound healing properties of the peptide.

Amino Acid Sequence↗
PubMed1992

[Modulation of the organization of the extracellular matrix and the production of collagen by interferon gamma in three-dimensional cultures of normal and sclerodermic fibroblasts].

Recent studies have shown inhibition of collagen synthesis by interferon gamma (IFN-gamma) in monolayer human fibroblast cultures on a plastic solid phase. However, the existence of this effect in vivo has not yet been demonstrated. Three-dimensional fibroblast cultures in collagen matrices (collagen lattices or dermal equivalents) provide a more physiological model than conventional cultures and fairly closely simulate in vivo conditions. This model was used for studying effects of IFN-gamma on normal and scleroderma fibroblasts. IFN-gamma induced a dose-dependent inhibition of fibroblast-mediated retraction of collagen lattices. IFN-gamma also inhibited total protein and collagen synthesis. Scleroderma fibroblasts were especially susceptible to the inhibitory effects of IFN-gamma. Since fibrotic scleroderma lesions are associated with tissue retraction and increased production of extracellular matrix macromolecules, these data confirm the potential value of IFN-gamma for the treatment of scleroderma and other fibrotic diseases.

Adult↗
PubMed1992

Gamma-interferon inhibits extracellular matrix synthesis and remodeling in collagen lattice cultures of normal and scleroderma skin fibroblasts.

Three-dimensional collagen lattice cultures of fibroblasts mimic the in vivo situation better than monolayer cultures. Here, skin fibroblasts from scleroderma patients and healthy controls were cultivated in collagen lattices, and the effects of recombinant human gamma-interferon (IFN-gamma) on these cultures investigated. IFN-gamma inhibited collagen lattice retraction in a dose-dependent way at concentrations ranging from 10 to 10,000 U/ml. This effect was independent of any alteration to the cell proliferation within the lattices. The inhibition was of the same order of magnitude in normal and pathological fibroblasts. The synthesis of collagen and non-collagen proteins, particularly fibronectin, was increased in scleroderma cultures. It was inhibited in both normal and scleroderma fibroblasts by IFN-gamma, with a maximal effect at the concentration 1000 U/ml, but the inhibition of protein synthesis was far more intense in scleroderma than in normal cells. In situ hybridization, Northern blot and dot blot analyses showed that mRNA coding for pro alpha 1(I) collagen was decreased in IFN-gamma-treated cells, indicating an effect at the pretranslational level. IFN-gamma also inhibited glycosaminoglycan synthesis, but in scleroderma cells only. This study shows that IFN-gamma regulates cell behavior in three-dimensional collagen matrices: (i) it decreases protein and specifically glycosaminoglycan synthesis in scleroderma fibroblasts, (ii) it modulates the interactions between cells and matrix that lead to the retraction of the lattice. Whereas collagen synthesis is largely decreased in lattice cultures like in vivo, it remains increased in the case of scleroderma compared to normal fibroblasts and may be down-regulated by IFN-gamma. Similar conclusions may be drawn for fibronectin and glycosaminoglycans. The inhibitory effect of IFN-gamma on the retraction capacity of fibroblasts and on their ability to synthesize increased amounts of extracellular matrix macromolecules may be of potential interest for therapeutic use of IFN-gamma in scleroderma patients.

Adult↗
PubMed1991

Effects of gamma irradiation on dermal equivalents in vitro.

Dermal equivalents (DE), collagen lattices, were produced in vitro and used as a model for studying the possible role of a pure population of fibroblasts in post-radiotherapeutic dermal fibrosis. Single doses of gamma irradiation induced a partial inhibition of the collagen lattice retraction and of protein synthesis. The collagen production was less inhibited than was synthesis of non-collagen protein, which resulted in an increase of the relative amount of collagen synthesized by irradiated fibroblasts. These data suggest that gamma irradiation might be able to select some fibroblast clones able to produce increasing amounts of collagen. This selection process could be involved in the development of tissue fibrosis after therapeutic radiation.

Animals↗
PubMed1991

The influence of some non-steroidal anti-inflammatory drugs on the retraction of collagen lattices.

The effects of some antirheumatics on the formation and retraction of collagen lattices seeded with fibroblasts have been studied. Among the antirheumatics, diclofenac was the most active inhibitor of lattice retraction, then tropesin and to a lesser extent indomethacin. Ibuprofen which is known as a very slight inhibitor of protein synthesis was able to significantly enhance lattice retraction when 10 micrograms/ml (48.5 microM) and 50 micrograms/ml (242 microM) were used.

Anti-Inflammatory Agents, Non-Steroidal↗
PubMed1991

Variability in the retraction of collagen lattices by scleroderma fibroblasts--relationship to protein synthesis and clinical data.

Skin fibroblasts from 18 scleroderma patients were seeded into collagen lattices and their ability to retract their substratum was compared with that of control fibroblasts from healthy donors. When considered as a whole, scleroderma fibroblasts retracted lattices earlier and more intensely than controls. Analysis of individual results demonstrated that morphea and diffuse systemic sclerosis (dSSc) fibroblasts had different kinetics of lattice retraction. Fibroblasts which contracted lattices more intensely than controls were found to produce increased levels of fibronectin. A comparison of the retraction of collagen lattices by fibroblasts from involved (IS) and uninvolved skin (US) of the same patients (n = 4) showed that those from IS retracted the lattices more than fibroblasts from normal donors, whereas a high variability was found with fibroblasts from US. The increased retraction of collagen lattices seems to be a feature of the more severe forms of scleroderma.

Adult↗
PubMed1991

Interleukin-4 stimulates collagen synthesis by normal and scleroderma fibroblasts in dermal equivalents.

Interleukin-4 (IL-4) is one of the products of T-lymphocytes and mast cells, inflammatory cells which accumulate in connective tissues at early stages of fibrosis. We tested the effects of IL-4 on human fibroblasts from normal and scleroderma skin seeded in three dimensional collagen lattices ("dermal equivalents"). IL-4 (10 and 100 U/ml) stimulated collagen synthesis in a dose-dependent manner. No significant alteration of lattice retraction and cell proliferation was observed. At the concentration 100 U/ml, Il-4 was approximately twice more efficient on collagen synthesis than Transforming Growth Factor beta (10 ng/ml). IL-4 secretion in connective tissues might be an important factor for the development of fibrotic processes.

Cells, Cultured↗
PubMed1990

Effect of transforming growth factor beta on fibroblasts in three-dimensional lattice cultures.

Human skin fibroblasts were cultivated in three-dimensional fibrin or collagen lattices, under retracting or non-retracting conditions, and the influence of transforming growth factor beta (TGF beta) was tested. TGF beta stimulated the synthesis of non-collagen protein and of collagen in all the systems. However, only in non-retracting fibrin lattices did it restore a level of protein synthesis comparable to that found in monolayers. The effects of TGF beta greatly depended on the type of substratum and on the presence or absence of retraction.

Cells, Cultured↗
PubMed1990

Stimulation of collagen synthesis in fibroblast cultures by a triterpene extracted from Centella asiatica.

The drug "Titrated Extract from Centella asiatica" (TECA), used for its stimulating properties on the healing of wounds, is a mixture of 3 terpenes extracted from a tropical plant: asiatic acid (30%, w/w), madecassic acid (30%, w/w) and asiaticoside (40%, w/w). The effects of TECA and its individual components were checked on human foreskin fibroblast monolayer cultures. TECA increased the collagen synthesis in a dose-dependent fashion whereas a simultaneous decrease in the specific activity of neosynthesized collagen was observed. Asiatic acid was found to be the only component responsible for collagen synthesis stimulation. TECA and all three terpenes increased the intracellular free proline pool. This effect was independent of the stimulation of collagen synthesis.

Cell Count↗