title: Transcriptional regulation of cyclooxygenase 2 by bradykinin and interleukin-1beta in human airway smooth muscle cells: involvement of different promoter elements, transcription factors, and histone h4 acetylation.
abstract: Bradykinin and interleukin-1beta (IL-1beta) induce cyclooxygenase 2 (COX-2) in human airway smooth muscle cells. Here we extended our study to explore the gene transcriptional regulation. By transfection with various COX-2 promoter reporter constructs, we found that the bp -327-to-+59 promoter region was essential for COX-2 gene transcription by bradykinin and IL-1beta and that the cyclic AMP response element (CRE) was critical in bradykinin-induced transcription, whereas nuclear factor IL-6 and CRE and, to a lesser extent, nuclear factor-kappaB (NF-kappaB) were involved in IL-1beta-induced transcription. An electrophoretic mobility shift assay revealed that both bradykinin and IL-1beta elicited CRE-binding protein-1 (CREB-1) binding, and IL-1beta also elicited CCAAT/enhancer-binding protein beta and NF-kappaB binding to their respective elements in the COX-2 promoter. These transcription factors were associated with the COX-2 promoter, which was dynamically linked to different patterns of histone H4 acetylation by bradykinin and IL-1beta, as demonstrated by chromatin immunoprecipitation. We also revealed that endogenous prostaglandin E(2) was critical in bradykinin-induced COX-2 transcription initiation and involved in IL-1beta-induced COX-2 transcription at a latter stage. Our result provide the first evidence that COX-2 transcriptional regulation by different stimuli involves different promoter elements and transcription factors and is associated with chromatin remodeling after selective histone H4 acetylation in a stimulus-specific manner.
authors.affiliation: Division of Respiratory Medicine, City Hospital, University of Nottingham, Hucknall Road, Nottingham NG5 1PB, United Kingdom. mszmn1@gwmail.nottingham.ac.uk
authors.forename: Mei
authors.initials: M
authors.lastname: Nie
authors.forename: Linhua
authors.initials: L
authors.lastname: Pang
authors.forename: Hiroyasu
authors.initials: H
authors.lastname: Inoue
authors.forename: Alan J
authors.initials: AJ
authors.lastname: Knox
mesh_terms: D000107:Acetylation; D021581:Active Transport, Cell Nucleus; D001483:Base Sequence; D001665:Binding Sites / Q000235:genetics; D001920:Bradykinin / Q000494:pharmacology*; D002478:Cells, Cultured; D017362:Cyclic AMP Response Element-Binding Protein; D051546:Cyclooxygenase 2; D004247:DNA / Q000235:genetics / Q000378:metabolism; D015232:Dinoprostone / Q000378:metabolism; D006657:Histones / Q000378:metabolism; D006801:Humans; D066298:In Vitro Techniques; D007375:Interleukin-1 / Q000494:pharmacology*; D007527:Isoenzymes / Q000235:genetics*; D008565:Membrane Proteins; D008954:Models, Biological; D008969:Molecular Sequence Data; D009130:Muscle, Smooth / Q000187:drug effects / Q000201:enzymology; D011401:Promoter Regions, Genetic; D011451:Prostaglandin-Endoperoxide Synthases / Q000235:genetics*; D012132:Respiratory Muscles / Q000187:drug effects / Q000201:enzymology; D014157:Transcription Factors / Q000378:metabolism; D014158:Transcription, Genetic / Q000187:drug effects; D014162:Transfection
chemical_list: C115163:CREB1 protein, human; D017362:Cyclic AMP Response Element-Binding Protein; D006657:Histones; D007375:Interleukin-1; D007527:Isoenzymes; D008565:Membrane Proteins; D014157:Transcription Factors; D004247:DNA; D051546:Cyclooxygenase 2; C496540:PTGS2 protein, human; D011451:Prostaglandin-Endoperoxide Synthases; D015232:Dinoprostone; D001920:Bradykinin