SDF-1alpha production is negatively regulated by mouse estrogen enhanced transcript in a mouse thymus epithelial cell line.
SDF-1/CXCR4 plays an important role in promoting survival, expansion, and differentiation of T cell progenitors. The present study investigates the mechanism by which estrogen inhibits SDF-1alpha expression in mouse thymus. Mouse estrogen enhanced transcript (mEET) is endogenously expressed in a mouse thymus epithelial cell line 1 (MTEC1). In MTEC1 cells that express the transfected sense mEET, the SDF-1alpha transcription and its chemotactic activity were profoundly inhibited. Conversely, in MTEC1 that express the transfected anti-sense mEET, the SDF-1alpha transcription and its chemotactic activity were substantially augmented. Moreover, we disclosed that mEET inhibited the production of SDF-1alpha by its suppression of NF-kappaB translocation into nucleus. Using a combinatorial induction of doxycycline (Dox) and 17beta-estradiol (E2) on the sense and anti-sense mEET transfectants, it was demonstrated that an increase of mEET expression enhanced E2-induced inhibition of SDF-1alpha production, while a blockade of mEET expression alleviated E2-induced inhibition of SDF-1alpha production. In conclusion, the E2-imposed suppression of SDF-1alpha production is partly mediated by mEET involved signaling pathway.
Jin
Cong
C
Department of Immunology, Peking University Health Science Centre, Beijing 100083, China.
Fu
Wen-Xian
WX
Xie
Lai-Ping
LP
Qian
Xiao-Ping
XP
Chen
Wei-Feng
WF
D000818:Animals; D002460:Cell Line; D054377:Chemokine CXCL12; D019743:Chemokines, CXC / Q000037:antagonists & inhibitors* / Q000096:biosynthesis* / Q000276:immunology; D002633:Chemotaxis / Q000276:immunology; D004318:Doxycycline / Q000276:immunology / Q000494:pharmacology; D004847:Epithelial Cells / Q000276:immunology / Q000378:metabolism; D004958:Estradiol / Q000276:immunology / Q000494:pharmacology*; D005260:Female; D005786:Gene Expression Regulation / Q000276:immunology; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D016328:NF-kappa B / Q000276:immunology; D010750:Phosphoproteins / Q000096:biosynthesis / Q000235:genetics / Q000276:immunology / Q000502:physiology*; D012333:RNA, Messenger / Q000096:biosynthesis / Q000235:genetics; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013950:Thymus Gland / Q000166:cytology / Q000187:drug effects / Q000276:immunology / Q000378:metabolism*; D014158:Transcription, Genetic / Q000276:immunology
D054377:Chemokine CXCL12; D019743:Chemokines, CXC; C515256:Cxcl12 protein, mouse; C107874:Litaf protein, rat; D016328:NF-kappa B; D010750:Phosphoproteins; D012333:RNA, Messenger; D004958:Estradiol; D004318:Doxycycline