Identification of cis-acting elements and signaling components of high affinity IgE receptor that regulate the expression of cyclooxygenase-2

Dong Im Cho, So Young Kim, Mei Zheng, Mingli Jin, Hoo Kyun Choi, Ae-Kyung Yi, Kyeong Man Kim

Research output: Contribution to journalArticle

4 Citations (Scopus)

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 Fc..RI, 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.

Original languageEnglish (US)
Pages (from-to)725-736
Number of pages12
JournalCellular Physiology and Biochemistry
Volume29
Issue number5-6
DOIs
StatePublished - Jan 1 2012

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IgE Receptors
Cyclooxygenase 2
Binding Sites
Mast Cells
CCAAT-Enhancer-Binding Protein-beta
MAP Kinase Signaling System
Mitogen-Activated Protein Kinase Kinases
Transcription Factor AP-1
p38 Mitogen-Activated Protein Kinases
Phosphatidylinositol 3-Kinases
Hypersensitivity

All Science Journal Classification (ASJC) codes

  • Physiology

Cite this

Identification of cis-acting elements and signaling components of high affinity IgE receptor that regulate the expression of cyclooxygenase-2. / Cho, Dong Im; Kim, So Young; Zheng, Mei; Jin, Mingli; Choi, Hoo Kyun; Yi, Ae-Kyung; Kim, Kyeong Man.

In: Cellular Physiology and Biochemistry, Vol. 29, No. 5-6, 01.01.2012, p. 725-736.

Research output: Contribution to journalArticle

Cho, Dong Im ; Kim, So Young ; Zheng, Mei ; Jin, Mingli ; Choi, Hoo Kyun ; Yi, Ae-Kyung ; Kim, Kyeong Man. / Identification of cis-acting elements and signaling components of high affinity IgE receptor that regulate the expression of cyclooxygenase-2. In: Cellular Physiology and Biochemistry. 2012 ; Vol. 29, No. 5-6. pp. 725-736.
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