PMID- 12355436 OWN - NLM STAT- MEDLINE DCOM- 20021127 LR - 20131121 IS - 0014-2980 (Print) IS - 0014-2980 (Linking) VI - 32 IP - 10 DP - 2002 Oct TI - Negative regulation of monocyte chemoattractant protein-1 gene expression by a mouse estrogen-enhanced transcript. PG - 2837-46 AB - A novel gene containing two typical estrogen responsive elements (ERE) was cloned from MTEC1 cells, a mouse thymus epithelial cell line that produces constitutively many chemokines. This gene is a homologue of the rat estrogen-enhanced transcript (EET) gene, and is called the mEET gene. mEET protein is expressed in cytoplasm. Addition of 17 beta-estradiol (E2) to the MTEC1 cell cultures enhanced mEET mRNA expression and, meanwhile, significantly inhibited monocyte chemoattractant protein-1 (MCP-1) production. To analyze the functional links between the expression of mEET and of MCP-1, we transfected MTEC1 cells with ERE-deleted antisense- or sense-mEET complementary (c)DNA construct and activated the transfected mEET cDNA in stable MTEC1 transfectants with doxycycline (Dox). Dox-induced activation of the mEET gene profoundly inhibited MCP-1 expression at both mRNA and protein levels and alleviated its chemotactic activity. Conversely, inactivation of the mEET gene substantially augmented MCP-1 expression. Activation of the mEET gene markedly attenuated activity of nuclear NF-kappaB. In summary, we have first demonstrated that estrogen-imposed inhibition of MCP-1 expression occurs through the activation of the mEET gene, its product suppresses nuclear NF-kappaB and negatively regulates MCP-1 gene activation. FAU - Xie, Lai-Ping AU - Xie LP AD - Department of Immunology, Peking University Health Science Centre, Beijing 100 083, China. FAU - Fu, Wen-Xian AU - Fu WX FAU - Jin, Cong AU - Jin C FAU - Dong, Xue-Yuan AU - Dong XY FAU - Chen, Wei-Feng AU - Chen WF LA - eng SI - GENBANK/AF171100 PT - Journal Article PT - Research Support, Non-U.S. Gov't PL - Germany TA - Eur J Immunol JT - European journal of immunology JID - 1273201 RN - 0 (Chemokine CCL2) RN - 0 (DNA, Complementary) RN - 0 (Litaf protein, rat) RN - 0 (NF-kappa B) RN - 0 (Phosphoproteins) RN - 0 (RNA, Messenger) RN - 4TI98Z838E (Estradiol) SB - IM MH - Amino Acid Sequence MH - Animals MH - Base Sequence MH - Cells, Cultured MH - Chemokine CCL2/biosynthesis/*genetics MH - DNA, Complementary/analysis MH - Estradiol/*pharmacology MH - Gene Expression Regulation/*drug effects MH - Mice MH - Mice, Inbred BALB C MH - Molecular Sequence Data MH - NF-kappa B/metabolism MH - Phosphoproteins MH - RNA, Messenger/analysis MH - Response Elements/*physiology MH - Transcription, Genetic MH - Transcriptional Activation MH - Transfection EDAT- 2002/10/02 04:00 MHDA- 2002/11/28 04:00 CRDT- 2002/10/02 04:00 PHST- 2002/10/02 04:00 [pubmed] PHST- 2002/11/28 04:00 [medline] PHST- 2002/10/02 04:00 [entrez] AID - 10.1002/1521-4141(2002010)32:10<2837::AID-IMMU2837>3.0.CO;2-V [doi] PST - ppublish SO - Eur J Immunol. 2002 Oct;32(10):2837-46. doi: 10.1002/1521-4141(2002010)32:10<2837::AID-IMMU2837>3.0.CO;2-V.