{"owner": "ArrayExpress Uploader", "pop_total": 0, "species": "human", "factors": [{"GSM654536": {"TREATMENT GROUP": "Unstimulated", "CELL TYPE": "Human primary lung fibroblast"}}, {"GSM654537": {"TREATMENT GROUP": "TNF-\u03b1 and IFN-\u03b3 stimulated", "CELL TYPE": "Human primary lung fibroblast"}}, {"GSM654538": {"TREATMENT GROUP": "Unstimulated", "CELL TYPE": "Human fetal lung fibroblast cell line"}}, {"GSM654539": {"TREATMENT GROUP": "TNF-\u03b1 and IFN-\u03b3 stimulated", "CELL TYPE": "Human fetal lung fibroblast cell line"}}, {"GSM654536": {"TREATMENT GROUP": "Unstimulated", "CELL TYPE": "Human primary lung fibroblast"}}, {"GSM654537": {"TREATMENT GROUP": "TNF-\u03b1 and IFN-\u03b3 stimulated", "CELL TYPE": "Human primary lung fibroblast"}}], "id": 3921, "ownerprofile_id": "arrayexpress_sid", "platform": 4, "summary_wrapped": "Idiopathic pulmonary fibrosis (IPF) is associated with the accumulation of collagen-secreting fibroblasts and myofibroblasts in the lung...", "geo_gse_id": "E-GEOD-26594", "owner_profile": "/profile/8773/arrayexpressuploader", "factor_count": 2, "sample_count": 6, "tags": ["basal", "cell", "collagen", "disease", "fibroblast", "idiopathic pulmonary fibrosis", "line", "lung", "lung parenchyma", "parenchyma", "pulmonary fibrosis"], "lastmodified": "Dec.12, 2014", "is_default": false, "geo_id_plat": "E-GEOD-26594_A-AFFY-44", "slug": "increased-cell-surface-fas-expression-is-necessary", "geo_gds_id": "", "name": "Increased Cell Surface Fas Expression is Necessary to Sensitize Lung Fibroblasts to Fas Ligation-Induced Apoptosis: Implications for Fibroblast Accumulation in Idiopathic Pulmonary Fibrosis.", "created": "Sep.15, 2014", "summary": "Idiopathic pulmonary fibrosis (IPF) is associated with the accumulation of collagen-secreting fibroblasts and myofibroblasts in the lung parenchyma. Many mechanisms contribute to their accumulation, including resistance to apoptosis. In previous work, we showed that exposure to the pro-inflammatory cytokines, TNF-\u03b1 and IFN-\u03b3 reverses fibroblast resistance to apoptosis. The goal of this study was to investigate the underlying mechanism. Based on an initial interrogation of the transcriptomes of unstimulated and TNF-\u03b1 and IFN-\u03b3-stimulated primary lung fibroblasts and the lung fibroblast cell line, MRC5, we show here that among Fas-signaling pathway molecules, Fas expression was increased ~6-fold in an NF-\u03baB and p38mapk-dependent fashion.  Prevention of the increase in Fas expression using Fas siRNAs blocked the ability of TNF-\u03b1 and IFN-\u03b3 to sensitize fibroblasts to Fas ligation induced-apoptosis; while enforced adenovirus-mediated Fas overexpression was sufficient to overcome basal resistance to Fas-induced apoptosis. Examination of lung tissues from IPF patients revealed low to absent staining of Fas in fibroblastic cells of fibroblast foci. Collectively, these findings suggest that increased expression of Fas is necessary and sufficient to overcome the resistance of lung fibroblasts to Fas-induced apoptosis. They also suggest that approaches aimed at increasing Fas expression by lung fibroblasts and myofibroblasts may be therapeutically relevant. To investigate the mechanism by which TNF-\u03b1 and IFN-\u03b3 reprogram fibroblasts from resistance to sensitivity to Fas-ligation-induce apoptosis, we exposed human primary lung fibroblasts from an IPF patient (FS087) and non-disease control subject (N78) and the human fetal lung fibroblast cell lung (MRC-5) to TNF-\u03b1 (10 ng/ml) and IFN-\u03b3 (50 U/ml) for 36 hr and analyzed changes in their transcriptomes using Affymetrix microarrays.", "source": "http://www.ebi.ac.uk/arrayexpress/experiments/E-GEOD-26594", "sample_source": "http://www.ebi.ac.uk/arrayexpress/experiments/E-GEOD-26594/samples/"}