title: The transcriptional activation of the cyclooxygenase-2 gene in zymosan-activated macrophages is dependent on NF-kappa B, C/EBP, AP-1, and CRE sites.
abstract: Zymosan is a yeast cell wall particle that activates several cell lines, especially macrophages, resulting in the stimulated secretion of inflammatory products including tumor necrosis factor alpha (TNF-α) and arachidonic acid. Cyclooxygenase-2 (COX-2) is an immediate early gene induced by several stimuli in macrophages. The following research aimed to investigate the regions of COX-2 promoter gene that mediate the inductive effects of zymosan. Transient transfections with a series of COX-2 promoter-mutation constructs were performed to further elucidate the effects of zymosan on COX-2 transcription. Exposure to zymosan (50 μg/mL for 24 h) markedly enhanced the relative luciferase activity in RAW 264.7 macrophages (mouse leukemic monocyte macrophage cell line) transfected with COX-2 luciferase promoter constructs. Deletion on the CCAAT-enhancer binding protein (C/EBP) and nuclear factor kappa B (NF-kappa B) binding site resulted in an important decrease in reporter gene activity and a deletion of NF-kappa B and C/EBP with mutation of the cyclic adenosine monophosphate response element (CRE) and/or activator protein-1 totally abolished the reporter gene activity induced by zymosan. These findings provide further insight into the signal transduction pathways involved in COX-2 gene activated by zymosan in macrophages.
authors.affiliation: Laboratório de Microbiologia Clínica, Ciências da Saúde, Centro Universitário Franciscano, UNIFRA, Santa Maria, Rio Grande do Sul, Brazil.
authors.forename: Roberto Christ Vianna
authors.initials: RC
authors.lastname: Santos
authors.forename: Miguel Angel Peña
authors.initials: MA
authors.lastname: Rico
authors.forename: Ramon
authors.initials: R
authors.lastname: Bartrons
authors.forename: Francesc Ventura
authors.initials: FV
authors.lastname: Pujol
authors.forename: Jose Luis
authors.initials: JL
authors.lastname: Rosa
authors.forename: Jarbas Rodrigues
authors.initials: JR
authors.lastname: de Oliveira
mesh_terms: D000818:Animals; D001665:Binding Sites; D022762:CCAAT-Enhancer-Binding Proteins; D002460:Cell Line; D017362:Cyclic AMP Response Element-Binding Protein; D051546:Cyclooxygenase 2 / Q000235:genetics*; D008264:Macrophages / Q000187:drug effects / Q000378:metabolism*; D051379:Mice; D016328:NF-kappa B; D011401:Promoter Regions, Genetic; D015398:Signal Transduction; D018808:Transcription Factor AP-1; D015533:Transcriptional Activation; D015054:Zymosan / Q000494:pharmacology*
chemical_list: D022762:CCAAT-Enhancer-Binding Proteins; D017362:Cyclic AMP Response Element-Binding Protein; D016328:NF-kappa B; D018808:Transcription Factor AP-1; D015054:Zymosan; C077623:Ptgs2 protein, mouse; D051546:Cyclooxygenase 2