Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UNIPROT:P04141 (granulocyte-macrophage colony-stimulating factor)
 6,790 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

A number of growth factors have been identified that participate in lung growth and repair. The early stages of the repair cascade are important in preventing the later development of fibrosis. Both transforming growth factor-beta and basic fibroblast growth factor can have beneficial effects when given early in some injury models. Keratinocyte growth factor stimulates type II cell hyperplasia in vitro but has not yet been studied in a lung injury model. Excessive production of growth factors such as transforming growth factor-alpha and transforming growth factor-beta can lead to fibrosis. Granulocyte-macrophage colony-stimulating factor is implicated in asthma, but now that knockout mice have been shown to have a histologic picture similar to pulmonary alveolar proteinosis, a new role for this factor in pulmonary disease has been suggested. Increasing our understanding of the diverse actions and interactions of growth factors in the lung will bring us closer to therapeutic interventions that can prevent some chronic lung diseases.
 ...
PMID:Role of growth factors in lung repair and diseases. 766 10

The ability to culture human thymic epithelial cells has greatly facilitated studies of direct cell-cell interaction between thymic epithelial cells and T lymphocytes in vitro, as well as cytokine production and regulation of cytokine production. In vitro, human thymic epithelial cells bind to T lymphocytes via two adhesion pathways: CD2-lymphocyte function-associated antigen-3 and lymphocyte function-associated antigen-1-intercellular adhesion molecule-1. Cultured human thymic epithelial cells produce interleukins-1 alpha, -1 beta, -3, -6 and -8, granulocyte colony-stimulating factor, macrophage colony-stimulating factor, granulocyte-macrophage colony-stimulating factor, leukemia inhibitory factor and transforming growth factor-alpha. Production of thymic epithelial cell-derived cytokines is regulated by both adhesion molecules (lymphocyte function-associated antigen-3) and soluble factors via both autocrine (interleukin-1 alpha, transforming growth factor-alpha) and paracrine (interleukin-4, interferon-gamma) pathways. Transforming growth factor-alpha and epidermal growth factor regulate various cytokine mRNA at a post-transcriptional level by increasing cytokine mRNA stability.
 ...
PMID:Human thymic epithelial cells: adhesion molecules and cytokine production. 851 15

Although epidemiological studies have shown that inorganic arsenicals are human skin carcinogens and induce hyperproliferation and hyperkeratosis, there is currently no known mechanism for their action or an established animal model for its study. We observed increased mRNA transcripts and secretion of keratinocyte growth factors, including granulocyte macrophage-colony stimulating factor (GM-CSF) and transforming growth factor-alpha (TGF alpha) and the proinflammatory cytokine tumor necrosis factor-alpha in primary human epidermal keratinocytes cultured in the presence of low micromolar concentrations of sodium arsenite. Treatment with sodium arsenite resulted in a significant increase in cell proliferation, as indicated by increases in cell numbers, c-myc gene expression, and incorporation of [3H]thymidine into cellular DNA. Studies of transcriptional regulation indicate that the rate of GM-CSF mRNA transcription is increased, while the elevated TGF alpha is likely the results of message stabilization. While a number of cytokine regulatory networks exist in the skin, studies utilizing neutralizing antibodies against the growth factors of interest indicate that inhibition of the arsenic-induced increase in TGF alpha results in a corresponding decrease in the gene expression and secretion of GM-CSF. The present studies demonstrate that growth-promoting cytokines and growth factors are induced in keratinocytes following treatment with arsenic and could play a significant role in arsenic-induced skin cancer.
 ...
PMID:Arsenic induces overexpression of growth factors in human keratinocytes. 891 4

The cytokines that regulate angiogenesis in normal and malignant prostate tissue are not well studied. Using an RT-PCR-based screen, we observed that cultured, low-passage normal human prostate epithelial cells (PrECs) express a variety of cytokines which have been shown to have angiogenic and/or endothelial cell-activating properties in various systems. These include vascular endothelial growth factor (VEGF), basic fibroblastic growth factor (bFGF), transforming growth factor-alpha (TGF-alpha), transforming growth factor-beta (TGF-beta), interleukin-8 (IL-8), tumor necrosis factor-alpha (TNF-alpha), granulocyte-macrophage colony-stimulating factor (GM-CSF) and granulocyte colony-stimulating factor (G-CSF). Expression of VEGF, bFGF, GM-CSF, G-CSF, TGF-alpha and TNF-alpha in these cells was confirmed by immunohistochemistry. Culture medium conditioned by normal human PrECs for periods of up to 96 hr were found to contain VEGF, GM-CSF, G-CSF, IL-8, TGF-beta1 and TGF-beta2 but not TNF-alpha or bFGF, as determined by ELISA. Of these, VEGF was by far the most prominently expressed angiogenic cytokine (approx. 2,500 pg/ml conditioned medium at 96 hr vs. 30 to 100 pg/ml conditioned medium for the other cytokines). PrEC-conditioned medium induced an approximately 2-fold stimulation of [3H]-thymidine incorporation in cultured human umbilical cord endothelial cells (HUVECs) deprived of the endothelial growth factors VEGF and bFGF; this stimulation was abolished by neutralizing antibodies directed against VEGF but not bFGF, IL-8, GM-CSF or TNF-alpha. VEGF expression by PrECs was not markedly altered by administration or deprivation of other angiogenic cytokines for which these cells have receptors, suggesting that there is not a hierarchy of cytokines controlling its expression; however, retinoic acid, a component of PrEC growth medium, was found to modestly suppress VEGF at physiological concentrations (0.1 ng/ml). These data suggest that normal PrECs express a variety of angiogenic cytokines, most prominently VEGF, to recruit a supporting vasculature, even in culture. Our data also suggest that the ability of malignant PrECs to stimulate angiogenesis may be intrinsic and does not need to be acquired during oncogenesis.
 ...
PMID:Expression of multiple angiogenic cytokines in cultured normal human prostate epithelial cells: predominance of vascular endothelial growth factor. 1007 20

The aim of the current study was to establish the epidermal growth factor receptor (EGFR) ligand expression profile in human airway epithelial cells exposed to either particulate matter (PM) with an aerodynamic diameter <2.5 microm (PM(2.5)) or its components and the involvement of EGFR ligands in PM(2.5)-provoked airway inflammation. EGFR ligand mRNA and protein expression were studied in a human bronchial epithelial cell line and normal nasal cells exposed to noncytotoxic concentrations of PM(2.5) or its components. The autocrine role of EGFR ligands in airway epithelial cell pro-inflammation was determined by adding conditioned media from PM(2.5)-treated cells to fresh cells and measuring the secretion of granulocyte-macrophage colony-stimulating factor (GM-CSF), a pro-inflammatory biomarker. PM(2.5)increased amphiregulin, transforming growth factor-alpha and heparin-binding EGF-like growth factor mRNA expression and protein secretion, with a slight contribution of aqueous metallic compounds and a strong participation of organic components putatively attributed to PM polyaromatic hydrocarbon content. PM(2.5)-induced EGFR ligands were involved in cellular GM-CSF release. The current study revealed upregulation of several epidermal growth factor receptor ligands by airway epithelial cells exposed to particulate matter with an aerodynamic diameter <2.5 microm and their contribution to bronchial epithelial cell granulocyte-macrophage colony-stimulating factor secretion by an autocrine action, suggesting that these ligands could elicit and sustain the particulate matter-induced airway pro-inflammatory response and contribute to bronchial remodelling.
 ...
PMID:Expression and role of EGFR ligands induced in airway cells by PM2.5 and its components. 1780 44

Biomarkers for treatment response would facilitate the testing of urgently needed new anti-tuberculous drugs. The present study investigated the profiles of 30 proinflammatory, anti-inflammatory and angiogenic factors [epidermal growth factor, eotaxin, fractalkine, granulocyte colony-stimulating factor, granulocyte-macrophage colony-stimulating factor, interleukin (IL)-1alpha, IL-1beta, IL-1ra, IL-2, IL-4, IL-5, IL-6, IL-7, IL-8, IL-10, IL-12p40, IL-12p70, IL-13, IL-15, IL-17, interferon-gamma, interferon-inducible protein-10, Krebs von den Lungen-6, monocyte chemotactic protein-1, macrophage inflammatory protein (MIP)-1alpha, MIP-1beta, sCD40L, transforming growth factor-alpha, tumour necrosis factor-alpha and vascular endothelial growth factor] in the plasma of 12 healthy tuberculin skin test-positive community controls and 20 human immunodeficiency virus-negative patients with active tuberculosis (TB) and identified potential biomarkers for early treatment response. We showed differences in the level of circulating cytokines between healthy controls and TB patients, but also between fast responders and slow responders to anti-tuberculosis treatment. The general discriminant analysis based on pre-treatment and week 1 measurements identified 10 sets of three-variable models that could classify fast and slow responders with up to 83% accuracy. Overall, this study shows the potential of cytokines as indicators of anti-tuberculosis treatment response.
 ...
PMID:Differential cytokine secretion and early treatment response in patients with pulmonary tuberculosis. 1919 52

Monocytes/macrophages and fibroblasts are recruited to the injury site and orchestrate the host response and tissue repair. We have previously shown that polyethylene glycol (PEG)-ylated arginine-glycine-aspartic acid (RGD) sequence grafted onto an extracellular matrix (ECM)-based semi-interpenetrating network (sIPN) enhances monocyte adhesion, and modulates subsequent gene expression and release of inflammatory and matrix remodeling factors. In this study, we investigate the direct influence of fibroblasts on monocyte response to this ECM mimic. Key wound-healing factors in inflammation, matrix remodeling, and regeneration were analyzed to gain insight into the interrelated role of regulation in fibroblast-monocyte interaction. Interleukin-1alpha/-1beta (IL-1alpha/-1beta), interleukin-6 (IL-6), tumor necrosis factor- alpha (TNF-alpha), monocyte inflammatory protein-1alpha/-1beta (MIP-1alpha/-1beta), transforming growth factor-alpha (TGF-alpha), monocyte chemoattractant factor (MCP-1), matrix metalloproteinase-2/-9 (MMP-2/-9), vascular endothelial growth factor (VEGF), granulocyte-macrophage colony-stimulating factor (GM-CSF) were analyzed. Fibroblasts decreased monocyte adhesion onto the RGD-grafted sIPN while increasing monocyte GM-CSF on all surfaces over time except for on RGD and PHSRN-grafted sIPN at 96 h. Monocytes decreased initial fibroblast IL-1alpha and TGF-alpha, but drastically increased fibroblast MMP-2 and GM-CSF. Monocyte IL-1beta, TNF-alpha, MIP-1beta, MCP-1, MMP-9, and GM-CSF expression was increased over time in the presence of all sIPNs, and when the sIPNs were immobilized with ligands, a down-regulation of fibroblast IL-1beta, MIP-1alpha, MIP-1beta compared with unmodified sIPN was observed. When the ligand immobilized was RGD, monocyte TGF-alpha, MIP-1beta, and VEGF expression was increased while monocyte GM-CSF was decreased at selected time points. These results showed a dynamic monocyte response to selected ECM components in the presence of fibroblasts.
 ...
PMID:Fibroblasts regulate monocyte response to ECM-derived matrix: the effects on monocyte adhesion and the production of inflammatory, matrix remodeling, and growth factor proteins. 1943 38