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

作者：Vianna Santos Roberto Christ; Pena Rico Miguel Angel; Bartrons Ramon; Ventura Pujol Francesc; Luis Rosa Jose; de Oliveira Jarbas Rodrigues^*

来源：Inflammation, 2011, 34(6): 653-658.

DOI：10.1007/s10753-010-9275-3

• zymosan
• COX-2
• luciferase
• macrophages

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-alpha) 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 mu g/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.

• 出版日期2011-12