title: Identification of cis-acting elements and signaling components of high affinity IgE receptor that regulate the expression of cyclooxygenase-2.
abstract: Allergic and inflammatory responses are functionally linked through a cascade of signaling events that connect the aggregation of the high affinity IgE receptor (FcεRI) on mast cells and the initiation of cyclooxygenase-2 (COX-2) expression. In this study, we identified the cis-acting elements in the cox-2 promoter that control the expression of COX-2 in RBL-2H3 mast cells. We also investigated how the inflammatory reaction is controlled by the allergic reaction by determining the signaling components employed by FcεRI in the transcriptional regulation of cox-2. Among cis-acting components present in the cox-2 promoter, the CREB binding site, as well as the AP-1 and proximal NF-IL6 binding sites to a lesser extent, were required for the transcriptional regulation of the cox-2 promoter. However, NF-κB and Ets-1 binding sites exerted negative effects on the cox-2 promoter activity. Among the signaling components of FcεRI, Fyn, PI 3-kinase, Akt, and p38 MAPK positively mediated the COX-2 expression. Conventional PKCs and atypical PKCs exerted opposite regulatory effects on the cox-2 promoter activity. Blockade of MEK/ERK pathway inhibited the cox-2 promoter activity and the COX-2 expression. These results reveal intricate functional interactions among different cis-acting elements in the transcriptional regulation of cox-2. Fyn-->PI 3-kinase-->Akt pathway directly stimulate. On the other hand, Lyn-->Syk pathway exerts auxiliary or compensatory influences on COX-2 expression via PKC and MEK/ERK.
authors.affiliation: Department of Pharmacology, College of Pharmacy, Chonnam National University, Gwang-Ju, Korea.
authors.forename: Dong-Im
authors.initials: DI
authors.lastname: Cho
authors.forename: So-Young
authors.initials: SY
authors.lastname: Kim
authors.forename: Mei
authors.initials: M
authors.lastname: Zheng
authors.forename: Mingli
authors.initials: M
authors.lastname: Jin
authors.forename: Hoo Kyun
authors.initials: HK
authors.lastname: Choi
authors.forename: Ae-Kyung
authors.initials: AK
authors.lastname: Yi
authors.forename: Kyeong-Man
authors.initials: KM
authors.lastname: Kim
mesh_terms: D000485:Allergens / Q000494:pharmacology; D000818:Animals; D001665:Binding Sites; D022782:CCAAT-Enhancer-Binding Protein-beta / Q000378:metabolism; D002460:Cell Line; D017362:Cyclic AMP Response Element-Binding Protein / Q000378:metabolism; D051546:Cyclooxygenase 2 / Q000378:metabolism*; D015971:Gene Expression Regulation, Enzymologic / Q000187:drug effects; D020935:MAP Kinase Signaling System; D009154:Mutation; D016328:NF-kappa B / Q000378:metabolism; D011401:Promoter Regions, Genetic; D051381:Rats; D017455:Receptors, IgE / Q000378:metabolism*; D015398:Signal Transduction; D018808:Transcription Factor AP-1 / Q000378:metabolism; D014158:Transcription, Genetic
chemical_list: D000485:Allergens; D022782:CCAAT-Enhancer-Binding Protein-beta; D017362:Cyclic AMP Response Element-Binding Protein; D016328:NF-kappa B; D017455:Receptors, IgE; D018808:Transcription Factor AP-1; D051546:Cyclooxygenase 2