Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0338671 (Steroids)
 9,479 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Accumulation of eosinophils in the bronchial tissue occurs in a variety of inflammatory disorders of the human airway. We asked whether airway epithelial cells released factors that could influence eosinophil survival and thus contribute to accumulation of these cells in the tissues. Using conditioned medium (CM) generated from cultured human bronchial epithelial cells (HBEC), we examined the in vitro survival of eosinophils isolated from human peripheral blood. When cultured in control medium, more than 90% of the eosinophils were dead by day 4. In contrast, culture in HBEC-CM resulted in dose-dependent survival at day 6 of 69 +/- 9.4%, 40.5 +/- 5.9%, and 25 +/- 2% viability with 2, 0.5, and 0.1% HBEC-CM, respectively (n = 4). Granulocyte/macrophage colony-stimulating factor (GM-CSF) was detected in the HBEC-CM by enzyme-linked immunosorbent assay at levels of 22 to 48 pg/ml. Furthermore, preincubation of the HBEC-CM with a neutralizing monoclonal antibody to human GM-CSF completely inhibited this increased survival of eosinophils. Because corticosteroids are potent eosinopenic agents, we also examined the effects of the synthetic steroid budesonide on this system. Budesonide inhibited both spontaneous and interleukin-1 (IL-1)-induced GM-CSF production by cultured HBEC. In addition, preincubation of eosinophils with budesonide caused marked abrogation of the survival induced subsequently with either HBEC-CM or recombinant human GM-CSF. In summary, HBEC can support eosinophil survival via the elaboration of GM-CSF and thus may contribute to the local control of inflammatory cell accumulation. Steroids may modulate this process both by inhibiting cytokine production from HBEC and by a direct effect on eosinophils, preventing their response to cytokines.
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PMID:Promotion of eosinophil survival by human bronchial epithelial cells and its modulation by steroids. 205 93

The c-fms proto-oncogene encodes the receptor for a hematopoietic growth factor, CSF-1. Recently, the importance of c-fms and its ligand CSF-1 in malignancies of non-hematopoietic origin, such as breast, ovarian, endometrial, pulmonary, and trophoblastic cancers has been recognized. We have previously shown that glucocorticoids induce a large increase in c-fms mRNA and protein levels in breast carcinoma cell lines. In this report, we investigate the mechanism underlying such c-fms overexpression by dexamethasone. We show that dexamethasone treatment of two breast carcinoma cell lines (BT20-c-fms expressor, and SKBR3-co-expressor of both c-fms and CSF-1) does not increase the rate of c-fms gene transcription, suggesting a post-transcriptional mechanism of regulation of c-fms expression by dexamethasone. The effect of protein synthesis inhibition was studied to help determine whether there was a role for intermediary regulatory proteins in the regulation of c-fms expression. We find that several protein synthesis inhibitors interfere with dexamethasone induction of c-fms transcripts, suggesting the existence of regulatory proteins. These regulatory proteins do not appear to be constitutively expressed, as we show no effect of protein synthesis inhibition on c-fms transcript expression in resting BT20 cells. These findings suggest that the putative regulatory proteins are induced by dexamethasone. Furthermore, the addition of a protein synthesis inhibitor, pactamycin, to dexamethasone-treated BT20 cells results in a decrease in c-fms mRNA stability.(ABSTRACT TRUNCATED AT 250 WORDS)
Steroids 1994 Sep
PMID:Post-transcriptional regulation of c-fms proto-oncogene expression by dexamethasone and of CSF-1 in human breast carcinomas in vitro. 784 33

Granulocyte/macrophage colony-stimulating factor (GM-CSF) is an important hematopoietic growth factor which has been shown to induce proliferation and activation of inflammatory cells, and may play a role in allergic diseases and experimental allergic reactions. Since little is known about the involvement of cytokines in allergic inflammation in the lung, we investigated whether human lung fragments produce GM-CSF in vitro. The present studies demonstrate that human lung fragments produce GM-CSF in vitro and that glucocorticoids are potent inhibitors of this cytokine production. Human lung was cut into fragments, rinsed, and cultured in 60-mm tissue culture plates containing 50 mg of tissue in RPMI 1640 with antibiotics in the presence or absence of a variety of steroids for 18 h. Lung fragments were rinsed and then incubated for an additional 4 h. Supernatants were harvested and analyzed for GM-CSF activity using the GM-CSF/interleukin (IL)-3 responsive M-07e human leukemic cell line. Steroids alone had no effect on M-07e proliferation. Human lung fragments produced 32.1 +/- 11.8 ng of GM-CSF equivalents per gram wet weight of tissue during the 4 h incubation (mean +/- S.E.M., n = 5, range 9.2-74.2). While specific antisera against human GM-CSF neutralized 96.8 +/- 2.8% (n = 5) of the activity, anti-IL-3 antibody had no effect, suggesting most or all of this activity was GM-CSF. Treatment of lung fragments in vitro for 18 h with hydrocortisone (HC) inhibited the production of GM-CSF dose-dependently. Maximal inhibition of GM-CSF production was 72.8 +/- 4.0% at a concentration of 10(-6) M hydrocortisone (n = 5), and the molar concentration of HC that inhibited of GM-CSF production by lung tissue by 50% (IC50) was approximately 4.5 x 10(-7) M. Kinetic studies revealed that a 6 h preincubation with the drug was required for 50% inhibition of GM-CSF production. HC and other glucocorticoids, at a concentration of 0.1 microM, demonstrated significant inhibition of GM-CSF release. Based on the rank order of potency of several glucocorticoids, and the fact that nonglucocorticoid steroids including testosterone and beta-estradiol (0.1 microM) had no effect, we suggest that this is a specific receptor-mediated effect. We conclude that human lung produces GM-CSF in vitro and that antiinflammatory steroids are potent and effective inhibitors of the production of this cytokine. This may contribute to the therapeutic efficacy of these drugs in pulmonary diseases.
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PMID:Antiinflammatory steroids inhibit granulocyte/macrophage colony-stimulating factor production by human lung tissue. 811 12