Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: HUMANGGP:031673 (collagen)
 124,196 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Analysis of cytokine mRNA and protein in rheumatoid arthritis tissue revealed that many proinflammatory cytokines such as TNF alpha, IL-1, IL-6, GM-CSF, and chemokines such as IL-8 are abundant in all patients regardless of therapy. This is compensated to some degree by the increased production of anti-inflammatory cytokines such as IL-10 and TGF beta and cytokine inhibitors such as IL-1ra and soluble TNF-R. However, this upregulation in homeostatic regulatory mechanisms is not sufficient as these are unable to neutralize all the TNF alpha and IL-1 produced. In rheumatoid joint cell cultures that spontaneously produce IL-1, TNF alpha was the major dominant regulator of IL-1. Subsequently, other proinflammatory cytokines were also inhibited if TNF alpha was neutralized, leading to the new concept that the proinflammatory cytokines were linked in a network with TNF alpha at its apex. This led to the hypothesis that TNF alpha was of major importance in rheumatoid arthritis and was a therapeutic target. This hypothesis has been successfully tested in animal models, of, for example, collagen-induced arthritis, and these studies have provided the rationale for clinical trials of anti-TNF alpha therapy in patients with long-standing rheumatoid arthritis. Several clinical trials using a chimeric anti-TNF alpha antibody have shown marked clinical benefit, verifying the hypothesis that TNF alpha is of major importance in rheumatoid arthritis. Retreatment studies have also shown benefit in repeated relapses, indicating that the disease remains TNF alpha dependent. Overall these studies demonstrate that analysis of cytokine expression and regulation may yield effective therapeutic targets in inflammatory disease.
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PMID:Role of cytokines in rheumatoid arthritis. 871 20

Pulmonary dendritic cells (DC) are present in extremely small numbers, but they are the most potent antigen-presenting cells in the lungs. Pure populations of DC can be isolated from the lung following collagen digestion, Percoll gradient centrifugation, removal of phagocytic cells and flow cytometric sorting for cells which exhibit high levels of surface major histocompatibility complex (MHC) class II molecules. Exogenous GM-CSF enhances this immunostimulatory capacity of the pulmonary DC. Soluble factors produced by type II airway epithelial cells and interstitial macrophages also enhance the immunostimulating capacity of pulmonary DC while alveolar macrophages suppress it. Thus, the function of DC may be regulated by locally produced cytokines. Corticosteroids are widely used as immunosuppressive agents in pharmacotherapy. While these agents are known to inhibit T cell proliferation and macrophage activation, their effects on DC are not known. We found that dexamethasone (Dex) pretreatment resulted in about a 50% reduction in the immunostimulatory capacity of rat pulmonary DC. This was associated with downregulation of MHC class II (Ia) expression. Dex-induced suppression of DC function could be restored with GM-CSF. We conclude that corticosteroids downregulate antigen-presenting capacity by direct suppression of pulmonary DC. This immunosuppressive effect of corticosteroids on DC may, however, be abrogated by exogenous GM-CSF. Corticosteroids and GM-CSF are therapeutic agents with potent direct immunomodulating effects on DC.
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PMID:Granulocyte-macrophage colony-stimulating factor overrides the immunosuppressive function of corticosteroids on rat pulmonary dendritic cells. 872 95

Nasal polyposis can be defined as a chronic inflammatory disease of the paranasal sinus mucosa, leading to a protrusion of benign edematous polyps from the meatus into the nasal cavities. Nasal polyps are histologically characterized by massive edema and accumulation of eosinophils. IgE-mediated allergy seems to play only a minor role in eosinophil accumulation, leaving the place for a new concept of non-allergic rhinitis with eosinophilia. The central question still remains, however, why eosinophils accumulate into nasal polyposis tissue. Some initial data show that tissue structural cells, i.e. epithelial cells or fibroblasts, could produce cytokines (GM-CSF) and play a role in eosinophil accumulation (micro-environmental theory). However, further studies showed, that GM-CSF was mainly produced by eosinophils themselves (autocrine theory), leading to the hypothesis of an intrinsic eosinophilic inflammatory process. Eosinophils may contribute to nasal polyp formation and growth not only through inflammation but also by exerting their effects on extracellular matrix including stimulation of collagen synthesis. Another feature associated with nasal polyposis is aspirin sensitivity. Some preliminary data indicate that eosinophils could also be involved in aspirin-sensitivity mechanisms.
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PMID:Eosinophils in the pathophysiology of nasal polyposis. 872 4

We previously identified a receptor for granulocyte colony-stimulating factor (G-CSFR) on platelet membranes, and reported that G-CSF enhanced ADP-induced platelet aggregation. Here, we investigated the priming effect of G-CSF on the hemostatic system in healthy volunteers given G-CSF. Following the administration of rhG-CSF (10 micrograms/kg for 30 min div) to 10 healthy volunteers, we found a significant elevation in the maximum platelet aggregation rate induced by ADP or collagen, thromboxane B2 level and amount of thrombin-antithrombin III complex. The D-D dimer and plasminogen activator inhibitor-1 showed no significant changes. These observations indicate that G-CSF administration may induce hypercoagulability in susceptible subjects. Therefore, patients or donors at risk of thrombosis or hypercoagulable state should be followed carefully after G-CSF administration.
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PMID:Effects of granulocyte colony-stimulating factor on the hemostatic system in healthy volunteers. 876 14

The morphologic and functional characteristics of cultured hair follicle dermal papilla (DP) cells, dermal sheath (DS) cells and interstitial dermal fibroblasts (DF cells) derived from human scalp tissue are compared. DP and DS cells, but not DF cells, showed aggregative behavior at a preconfluent density. All three types of cells stained positive for type I collagen, type IV collagen, laminin and heparan sulfate proteoglycan. Only DP and DS cells expressed smooth muscle alpha-actin. DP and DS cells also synthesized more glycosaminoglycans (GAG) than DF cells, while there was no significant difference between DP and DS cells in GAG synthesis. Ultrastructurally, 7 out of 10 strains of DP and 2 out of 10 strains of DS cells were found to form intranuclear rodlets, while none of the 10 strains of DF cells examined formed intranuclear rodlets. The conditioned medium of the three types of cells was collected and tested for the presence of interleukin (IL)-1 beta, tumor necrosis factor (TGF)-beta 2, IL-6, platelet-derived growth factor-AB, epidermal growth factor, b-FGF, GM-CSF, insulin-like growth factor (IGF)-1 and HGF (hepatocyte growth factor) by ELISA or RIA. Among the tested cytokines and growth factors, TGF-beta 2, IL-6 and IGF-I were detectable in at least some conditioned media. The others were undetectable. There was no significant difference in the production of IL-6 and IGF-I among the three types of cells. In contrast, DP cells produced the highest levels of TGF-beta 2, DS cells produced intermediate levels of TGF-beta 2, and DF cells produced the lowest levels of TGF-beta 2. DP and DS cells are morphologically and functionally different from the nonfollicular, interstitial DF cells. Moreover, the presence of some minor biologic differences between DP and DS cells suggests that they represent follicular mesenchymal cells in different functional or differentiation states.
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PMID:Human hair follicle dermal papilla cell, dermal sheath cell and interstitial dermal fibroblast characteristics. 891 54

Human monocyte/macrophages (Mphi) were adhered to extracellular matrix proteins, and the intracellular growth of Histoplasma capsulatum (Hc) yeasts were quantified and compared with their growth in Mphi adhered to plastic. Freshly isolated monocytes and cultured monocyte/derived Mphi adhered to type 1 collagen gels, but not to nongelled collagen-, fibronectin-, laminin-, or vitronectin-coated surfaces, demonstrated significant fungistatic activity against Hc yeasts. Activation of Mphi developed immediately upon adherence to the collagen matrices (1 h) and did not require additional time in culture. In addition, many of the yeasts were digested by 24 h postinfection. Mphi adhered to collagen maintained their fungistatic activity for up to 4 days, during which time monolayers cultured on plastic were destroyed. Culture of Mphi in the presence of IFN-gamma or TNF-alpha for 24 h before infection did not augment the fungistatic activity of collagen-adherent Mphi. Likewise, culture of monocytes on collagen gels with IL-3, granulocyte-Mphi CSF (GM-CSF) or Mphi CSF (M-CSF) for 7 days did not enhance Mphi fungistatic activity above that obtained by monocytes cultured on collagen alone. The mechanism(s) of Mphi-mediated fungistasis was not associated with production of toxic oxygen radicals, nitric oxide, or the restriction of intracellular iron. However, experiments with horseradish peroxidase-labeled gold colloids and immunoelectron microscopy demonstrated that phagolysosomal fusion, which is minimal in Hc-infected Mphi adhered to plastic, is enhanced significantly at both 1 h and 24 h postinfection in Mphi adhered to collagen matrices. These data suggest that in vivo, matrix-bound Mphi may express a previously unrecognized antifungal activity that proceeds in the absence of exogenous cytokines and is mediated, in part, by overcoming the capacity of Hc yeasts to inhibit Mphi phagolysosomal fusion.
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PMID:Activation of human macrophage fungistatic activity against Histoplasma capsulatum upon adherence to type 1 collagen matrices. 902 16

We performed a retrospective review of 78 consecutive neurosurgical procedures using Vicryl Collagen, a resorbable mesh of polyglactin 910 coated with bovine collagen, for dural substitution. The complications we encountered were infrequent and mostly minor (5 cases of subcutaneous CSF collections, 2 cases of aseptic meningitis, 1 superficial wound infection), and not unusual for the surgical procedures studied. One patient, however, had a major infection, starting in the superficial tissues, and extending toward the brain. In this patient, the resorption of the dural substitute appeared to be the cause for the intracranial extension of the infection. Three patients were reoperated on for recurrent tumour after a longer interval. We found minimal adhesions and good fibrous incorporation of the Vicryl Collagen into the surrounding normal dura. We conclude that Vicryl Collagen is a valuable alternative to the patient's own fibrous tissues when dural substitution is necessary.
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PMID:The use of Vicryl Collagen as a dura substitute: a clinical review of 78 surgical cases. 908 69

The conditions that control the migratory status of hematopoietic progenitor cells on extracellular matrix (ECM) and that decide whether a cell migrates or adheres are incompletely understood. We analyzed the migratory behavior of murine hematopoietic progenitor cells factor-dependent-cell-paterson (FDCP)-mix and purified lin-Sca1+ bone marrow cells on ECM. We found that migration on fibronectin (Fn) or laminin (Lam) becomes dependent on beta1-integrins if a surface restraint force is introduced by tilting the ECM-coated culture vessels. Under these conditions, migration specifically occured on Fn and Lam, and was not detected on collagen IV-, hyaluronate-, or bovine serum albumin- coated surfaces. Migration depended on the continuous presence of hematopoietic cytokines interleukin-3 (IL-3), granulocyte colony-stimulating factor (G-CSF), macrophage-CSF (M-CSF), granulocyte-macrophage-CSF (GM-CSF), or stem cell factor (SCF), whereas other cytokines, such as IL-8, macrophage inflammatory protein-1alpha, macrophage-chemotactic and activating factor, and erythropoietin resulted in very little or no migratory response. IL-3 induced migration was synergistically enhanced by other CSFs, but was completely inhibited by addition of transforming growth factor-beta1. In contrast to firm local adhesion of previously cytokine depleted progenitors that was rapidly inducible within 1 hour after exposure to cytokines, preincubation on Fn matrix for 4 to 6 hours was required before cytokines could induce migration. A sudden increase of cytokine concentration reversibly inhibited migration and induced a fully adhesive state; this effect could be prolonged by consecutive stimulation with heterologous cytokines. Whereas cytokines activated resting progenitor cells to migrate on ECM, cell migration speed was regulated by Fn concentration. These results indicate that beta1-integrin-mediated progenitor cell adhesion and migration are differentially regulated by external stimuli and suggest that this regulation corresponds to different activation states of beta1-integrins in hematopoietic progenitor cells.
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PMID:Adhesion and migration are differentially regulated in hematopoietic progenitor cells by cytokines and extracellular matrix. 934 36

The study of liver dendritic cells (DC) and their progenitors is restricted by the small numbers that can be isolated or propagated from normal hepatic tissue. We examined the ex vivo growth, phenotype, and function of these cells after the administration to mice of the recently cloned hemopoietic growth factor flt3 ligand (FL), which is highly effective in mobilizing stem/progenitor cells. FL treatment (10 microg/day for 10 days) resulted in a mean 14-fold increase in the absolute number of nonparenchymal cells recovered from collagenase-digested livers compared with the control value. Culture of these nonparenchymal cells in granulocyte-macrophage CSF (GM-CSF; 1000 U/ml) resulted in the early formation of proliferating cell clusters and maximal release (within 4-5 days) of markedly increased numbers of nonadherent, low buoyant density cells per liver. Maximal release of low buoyant density cells propagated from control livers was at the later time of 6 to 8 days. Cells from both sources were DEC-205+, CD11c+, MHC class II+, CD80(low) (i.e., low level of CD80), CD86(low) and CD40(low). This immature phenotype was linked to poor T cell allostimulatory activity, indicative of DC progenitors. Propagation of cells from livers of FL-treated mice in GM-CSF and IL-4 resulted in a more mature DC phenotype and function. Maturational changes were also observed following exposure of the GM-CSF-stimulated progenitors to type 1 collagen for 3 additional days. The ability of FL to boost production of large numbers of liver DC progenitors provides opportunities for the further study of these important APC in normal liver immunobiology and in immune-mediated hepatic disorders.
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PMID:In vivo administration of flt3 ligand markedly stimulates generation of dendritic cell progenitors from mouse liver. 937 22

We recently described a novel population of blood-borne cells, termed fibrocytes, that display a distinct cell surface phenotype (collagen+/CD13+/CD34+/CD45+), rapidly enter sites of tissue injury, and contribute to scar formation. To further characterize the role of these cells in vivo, we examined the expression of type I collagen and cytokine mRNAs by cells isolated from wound chambers implanted into mice. Five days after chamber implantation, CD34+ fibrocytes but not CD14+ monocytes or CD90+ T cells expressed mRNA for type I collagen. Fibrocytes purified from wound chambers also were found to express mRNA for IL-1beta, IL-10, TNF-alpha, JE/MCP, MIP-1alpha, MIP-1beta, MIP-2, PDGF-A, TGF-beta1, and M-CSF. The addition of IL-1beta (1-100 ng/ml), a critical mediator in wound healing, to fibrocytes isolated from human peripheral blood induced the secretion of chemokines (MIP-1alpha, MIP-1beta, MCP-1, IL-8, and GRO alpha), hemopoietic growth factors (IL-6, IL-10, and macrophage-CSF), and the fibrogenic cytokine TNF-alpha. By contrast, IL-1beta decreased the constitutive secretion of type I collagen as measured by ELISA. Additional evidence for a role for fibrocytes in collagen production in vivo was obtained in studies of livers obtained from Schistosoma japonicum-infected mice. Mouse fibrocytes localized to areas of granuloma formation and connective matrix deposition. We conclude that fibrocytes are an important source of cytokines and type I collagen during both the inflammatory and the repair phase of the wound healing response. Furthermore, IL-1beta may act on fibrocytes to effect a phenotypic transition between a repair/remodeling and a proinflammatory mode.
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PMID:Regulated production of type I collagen and inflammatory cytokines by peripheral blood fibrocytes. 955 99


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