Interferon-Tau Suppresses Prostaglandin F2α Secretion Independently of the Mitogen-Activated Protein Kinase and Nuclear Factor κ B Pathways1
Interferon-Tau Suppresses Prostaglandin F2α Secretion Independently of the Mitogen-Activated Protein Kinase and Nuclear Factor κ B Pathways1
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干扰素 Tau 抑制前列腺素 F2α 分泌，独立于丝裂原激活蛋白激酶和核因子 κ B 通路1
DOI：
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发表时间：
2001
期刊：
影响因子：
--
通讯作者：
T. R. Hansen
中科院分区：
文献类型：
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作者：
J. Pru;B. Rueda;K. Austin;W. Thatcher;A. Guzeloglu;T. R. Hansen
反刍动物妊娠是通过干扰素-τ抑制前列腺素F2α（PGF）的释放，使黄体存活并继续产生孕酮而实现的。设计实验以1）描绘协调PGF合成的信号转导途径，2）确定重组牛（rb）IFN-τ减弱佛波酯（PDBu）诱导的PGF分泌的速度，和3）建立rbIFN-τ减弱培养的牛子宫内膜（弯曲）细胞中PGF分泌的位点。弯曲细胞未处理（对照）或用PDBu（100 ng/ml）、rbIFN-τ（50或500 ng/ml）、PDBu + rbIFN-τ或PDBu + PD 98059（MEK-1抑制剂; 50 μM）处理5、10、60、180或300 min。PDBu在180 min内可诱导PGF分泌（P < 0.0001），而rbIFN-τ可抑制PGF分泌74%（P < 0.0001），PD 98059可完全阻断PGF分泌。环氧合酶（考克斯）-2蛋白表达也获得了类似结果。PDBu诱导（P < 0.05）Raf-1/MEK-1/ERK-1/2通路的激活，该通路是考克斯-2表达和PGF分泌的必需通路，但与rbIFN-τ共同处理对该通路无影响。PDBu在30 min内诱导c-jun和c-fos mRNA的转录（P < 0.05），PD 98059可抑制PDBu的诱导作用（P < 0.05），而rbIFN-τ则无此作用。用rbIFN-τ处理弯曲细胞也没有减弱PDBu-I κBα的降解，这表明IκBα/NFκB途径不是IFN-τ抑制PGF的位点。总之，PDBu诱导的考克斯-2表达和PGF分泌是通过Raf-1/MEK-1/ERK-1/2途径介导的，但该途径不被rbIFN-τ破坏。由于rbIFN-τ在30分钟内抑制考克斯-2 mRNA，我们推测rbIFN-τ激活的转录因子快速直接减弱考克斯-2基因表达，从而抑制PGF分泌。
Abstract Pregnancy is established in ruminants through inhibitory actions of interferon (IFN)-τ on the release of prostaglandin F2α (PGF), which allows the corpus luteum to survive and continue to produce progesterone. Experiments were designed to 1) delineate the signal transduction pathway coordinating the synthesis of PGF, 2) determine how rapidly recombinant bovine (rb) IFN-τ attenuated phorbol ester (PDBu)-induced secretion of PGF, and 3) establish the site at which rbIFN-τ attenuates the secretion of PGF in cultured bovine endometrial (BEND) cells. BEND cells were untreated (control) or treated for 5, 10, 60, 180, or 300 min with PDBu (100 ng/ml), rbIFN-τ (50 or 500 ng/ml), PDBu + rbIFN-τ, or PDBu + PD98059 (MEK-1 inhibitor; 50 μM). Secretion of PGF was induced (P < 0.0001) by PDBu within 180 min, but induction was inhibited 74% by the addition of rbIFN-τ (P < 0.0001) and was ablated completely by PD98059. Parallel results were obtained for cyclooxygenase (COX)-2 protein expression. PDBu induced (P < 0.05) activation of the Raf-1/MEK-1/ERK-1/2 pathway, which was obligatory for the expression of COX-2 and secretion of PGF but was not altered by cotreatment with rbIFN-τ. PDBu induced (P < 0.05) transcription of c-jun and c-fos mRNAs within 30 min; induction was inhibited (P < 0.05) by cotreatment with PD98059 but not by cotreatment with rbIFN-τ. Treatment of BEND cells with rbIFN-τ also did not attenuate PDBu-induced degradation of IκBα, suggesting that the IκBα/NFκB pathway is not a site of IFN-τ inhibition of PGF. However, rbIFN-τ did block transcription of the COX-2 gene induced by PDBu within 30 min. In conclusion, COX-2 expression and PGF secretion induced by PDBu is mediated through the Raf-1/MEK-1/ERK-1/2 pathway, but this pathway is not disrupted by rbIFN-τ. Because rbIFN-τ inhibits COX-2 mRNA within 30 min, we hypothesized that transcription factors activated by rbIFN-τ rapidly and directly attenuate COX-2 gene expression, thereby suppressing secretion of PGF.
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催产素刺激牛子宫内膜子宫 PGF2 α 合成的细胞机制：磷脂酶 C 和 A2 的作用。
影响因子：
2.1
作者：
Burns,PD;Graf,GA;Hayes,SH;Silvia,WJ
通讯作者：
Silvia,WJ
干扰素-tau 复合诱导牛子宫蛋白。
影响因子：
3.6
作者：
Staggs,KL;Austin,KJ;Johnson,GA;Teixeira,MG;Talbott,CT;Dooley,VA;Hansen,TR
通讯作者：
Hansen,TR
家养反刍动物黄体孕酮合成的分子调控。
DOI：
--
发表时间：
1999
期刊：
Journal of reproduction and fertility. Supplement.
影响因子：
--
作者：
Juengel,JL;Niswender,GD
通讯作者：
Niswender,GD
在子宫内用重组牛干扰素 tau 进行治疗可减弱培养的子宫内膜上皮细胞对前列腺素 F 的分泌。
影响因子：
3.5
作者：
Meyer,MD;Desnoyers,GD;Oldick,B;Thatcher,WW;Drost,M;Schalue,TK;Roberts,RM
通讯作者：
Roberts,RM
干扰素刺激基因 17 的克隆：调节转录的启动子和核蛋白。
DOI：
10.1210/mend.13.7.0294
发表时间：
1999
期刊：
Molecular endocrinology (Baltimore, Md.)
影响因子：
--
作者：
Perry,DJ;Austin,KJ;Hansen,TR
通讯作者：
Hansen,TR