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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

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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.

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Acknowledgments

This study was supported by grants from CAPES/DGU (BEX 4422/09-0)—Brazil, IDIBELL (Institut d'Investigació Biomèdica de Bellvitge) and Secretaría de Estado de Universidades, Ministerio de Ciencia e Innovación (PHB2008-0080-PC)—Spain.

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Authors and Affiliations

  1. Laboratório de Microbiologia Clínica, Ciências da Saúde, Centro Universitário Franciscano, UNIFRA, Santa Maria, Rio Grande do Sul, Brazil

    Roberto Christ Vianna Santos

  2. Laboratório de Biofísica Celular e Inflamação, Pontifícia Universidade Católica do Rio Grande do Sul, PUCRS, Santa Maria, Rio Grande do Sul, Brazil

    Roberto Christ Vianna Santos & Jarbas Rodrigues de Oliveira

  3. Departament de Ciències Fisiològiques II, IDIBELL, Universitat de Barcelona, Campus de Bellvitge, Barcelona, Spain

    Roberto Christ Vianna Santos, Miguel Angel Peña Rico, Ramon Bartrons, Francesc Ventura Pujol, Jose Luis Rosa & Jarbas Rodrigues de Oliveira

  4. Laboratório de Pesquisa em Biofísica Celular e Inflamação, Pontifícia Universidade Católica do Rio Grande do Sul (PUCRS), Avenida Ipiranga 6681, prédio 12, bloco C, sala 263, 90.619-900, Porto Alegre, Rio Grande do Sul, Brazil

    Jarbas Rodrigues de Oliveira

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  1. Roberto Christ Vianna Santos
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  2. Miguel Angel Peña Rico
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Correspondence to Jarbas Rodrigues de Oliveira.

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Santos, R.C.V., Rico, M.A.P., Bartrons, R. et al. 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. Inflammation 34, 653–658 (2011). https://doi.org/10.1007/s10753-010-9275-3

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  • DOI: https://doi.org/10.1007/s10753-010-9275-3

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