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

Interleukin-1 (IL-1) may have a significant pro-inflammatory effect in the skin; an imbalance in its production has been linked to cutaneous disease processes. IL-1 receptor antagonist (IL-1ra) is a recently described competitive inhibitor of IL-1 alpha and IL-1 beta that binds to human types I and II IL-1 receptors without apparent cell activation. Human keratinocytes synthesize IL-1ra, IL-1 alpha, and IL-1 beta but fail to secrete these cytokines. This study investigated IL-1ra and IL-1 alpha accumulation by cultured keratinocytes stimulated by tumor necrosis factor-alpha (TNF-alpha), IL-3, IL-4, IL-6, IL-10, interferon-gamma, granulocyte-macrophage colony-stimulating factor, granulocyte colony-stimulating factor, and macrophage colony-stimulating factor and by various extracellular matrix proteins, conditions that these cells may encounter in normal or inflamed skin in vivo. IL-1ra and IL-1 alpha proteins were measured by specific enzyme-linked immunosorbent assay in keratinocyte supernatants and lysates. Only TNF-alpha induced IL-1ra and IL-1 alpha production. TNF-alpha added to culture in amounts of 10 ng/ml or higher, induced a twofold increase in intracellular levels of both IL-ra and IL-1 alpha without secretion at 48 h. The IL-1ra concentration in keratinocyte lysates increased from 9.6 to 17.6 ng/ml after TNF-alpha stimulation, and the IL-1 alpha concentration increased from 1.0 to 3.3 ng/ml. Keratinocytes also exhibited comparable increases in IL-1 alpha and IL-1ra mRNA levels after 12 h in culture with TNF-alpha, as determined by in vitro hybridization to specific cDNA probes. The IL-1 alpha and IL-1ra response to TNF-alpha stimulation showed a varied pattern among different keratinocyte strains over 72 h of culture on plain plastic. In contrast, extracellular matrix proteins (laminin, fibronectin, collagen I and IV, and vitronectin) did not stimulate keratinocyte accumulation of IL-1 alpha or IL-1ra proteins after 72 h in culture. When TNF-alpha was added to cells cultured on these matrices, no change in IL-1 alpha or IL-1ra production was observed above that which could be attributed to TNF-alpha alone. In conclusion, TNF-alpha, but not the extracellular matrix proteins tested, stimulated production of intracellular IL-1 alpha and IL-1ra by keratinocytes. The ratio of IL-1ra to IL-1 alpha after TNF-alpha stimulation of keratinocytes may influence the inflammatory profile in the epidermis.
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PMID:Tumor necrosis factor-alpha induces interleukin-1 alpha and interleukin-1 receptor antagonist production by cultured human keratinocytes. 833 Dec 99

Macrophage colony-stimulating factor (M-CSF) is essential for murine osteoclast formation and its role in human hematopoiesis in vitro is not fully defined. Therefore, we have investigated the effect of M-CSF on the formation of human osteoclasts in vitro. M-CSF was found to induce substantial bone resorption and osteoclast formation in a dose-responsive and time-dependent manner above that induced by 1,25 dihydroxyvitamin D3 (1,25 vitamin D3) in cultures of human bone marrow (BM) stromal cells sedimented onto devitalized bone. By day 14 there was a mean of approximately 50% of the surfaces of the bone slices resorbed compared with only 6% in cultures treated with 1,25 vitamin D3 alone. Osteoclasts were identified as 23c6+ cells (an antibody that recognizes the vitronectin receptor), 87.5% of which coexpressed the calcitonin receptor. The number of 23c6+ cells correlated strongly with bone resorption spatially, and in a dose-responsive and time-dependent manner; the correlation coefficient in cultures treated with 1,25 vitamin D3 alone was 0.856 and those treated with both M-CSF and 1,25 vitamin D3 was 0.880. Granulocyte-macrophage colony-stimulating factor, IL-1 beta, IL-3, IL-6, tumor necrosis factor-alpha, transforming growth factor-beta, leukemia inhibitory factor, and IL-11 did not increase bone resorption above that in 1,25 vitamin D3-treated cultures. We also found that 1,25 vitamin D3 increased, to a minor but significant degree, both bone resorption and the concentration of M-CSF in the culture supernatants above that in vehicle-treated cultures, indicating that M-CSF is present in our BM cultures, but that there is insufficient to induce substantial osteoclast formation. These results define a critical role for M-CSF in the formation of human osteoclasts.
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PMID:Macrophage colony-stimulating factor induces substantial osteoclast generation and bone resorption in human bone marrow cultures. 883 45

The formation of multinucleated giant cells (MGCs) from monocytes/macrophages is controlled by various cytokines whose crucial roles are not fully understood. In this study, we found that interleukin (IL)-13 as well as IL-4 induced peripheral blood monocytes (PBMs) and monoblastic cell line, UG3, to differentiate into MGCs in the presence of macrophage colony-stimulating factor (M-CSF), while IL-2, IL-7 or IL-10 did not. The presence of M-CSF was essential to this MGC formation, because IL-3 or granulocyte-macrophage colony-stimulating factor (GM-CSF) could not replace M-CSF. IL-4 and IL-13 have been known to inhibit the formation of osteoclast-like cells in the presence of stroma cells or osteoblastic cells. But in our system without stroma cells, IL-4 or IL-13 induced some of characteristics of osteoclasts such as tartrate-resistant acid phosphatase (TRAP) activity, vitronectin receptor (vit-R) expression and resorptive activity for hydroxyapatite, but not the expression of receptors for parathyroid hormone or calcitonin. These results suggest possible involvement of IL-4 and IL-13 in MGCs and osteoclasts development, and UG3 may be useful to further investigate the roles of IL-4 and IL-13 in the formation and physiology of MGCs, and the relationship between these MGCs and osteoclasts.
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PMID:IL-13 as well as IL-4 induces monocytes/macrophages and a monoblastic cell line (UG3) to differentiate into multinucleated giant cells in the presence of M-CSF. 987 26

Engagement of integrin receptors during cell adhesion leads to changes in the morphology and the state of activation of cells. We therefore examined whether mast cell adhesion to extracellular matrix proteins affects the synthesis and release of various proinflammatory cytokines. Cells of the human mast cell line HMC-1 were added to fibronectin (FN)-, vitronectin (VN)- or, as a control, bovine serum albumin (BSA)-coated wells and were stimulated with phorbol 12-myristate 13-acetate (PMA) and/or calcium ionophore A23187 (ionophore). Cytokine production was evaluated using semiquantitative reverse transcription-polymerase chain reaction (RT-PCR) analysis of cell extracts and enzyme-linked immunosorbent assay (ELISA) analysis of cell supernatants. After a 4-hr incubation, mRNA expression of interleukin (IL)-8 (and weakly of IL-6) was up-regulated in matrix-adherent cells, with further increase in the presence of PMA and/or ionophore, compared with unstimulated cells. High-level de novo expression of IL-3 and of granulocyte-macrophage colony-stimulating factor (GM-CSF) was observed mainly in matrix-adherent cells. These changes were paralleled by the secretory pattern of HMC-1 cells after a 24-hr stimulation. Unstimulated cells adherent to FN or VN had already released small amounts of IL-8, and both VN- and FN-adherent cells produced, almost invariably, a higher level of cytokines than BSA-exposed cells after additional stimulation. These results show that mast cell adhesion to matrix proteins by itself has only selected and minor effects, but additional activation of mast cells by secretory stimuli causes significantly enhanced cytokine gene expression and secretion, suggesting that mast cells are far more active in their natural tissue environment than hitherto suggested from data in suspension cultures.
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PMID:Adhesion of human mast cells to extracellular matrix provides a co-stimulatory signal for cytokine production. 1054 Feb 24