IL-6 trans-signaling system in intra-amniotic inflammation, preterm birth, and preterm premature rupture of the membranes.
IL-6 trans-signaling system in intra-amniotic inflammation, preterm birth, and preterm premature rupture of the membranes.
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DOI：
10.4049/jimmunol.1003587
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发表时间：
2011-03-01
期刊：
影响因子：
--
通讯作者：
Buhimschi CS
中科院分区：
文献类型：
--
作者：
Lee SY;Buhimschi IA;Dulay AT;Ali UA;Zhao G;Abdel-Razeq SS;Bahtiyar MO;Thung SF;Funai EF;Buhimschi CS
经典的IL-6信号传导受跨膜受体（IL-6 R）和gp 130的同源二聚化的调节。在反式信号传导过程中，IL-6与可溶性IL-6 R（sIL-6 R）结合，从而激活仅表达gp 130的细胞。可溶性gp 130（sgp 130）选择性抑制IL-6反式信号传导。表征羊水IL-6反式信号分子我们对301例正常妊娠及合并羊膜内炎症（IAI）的妊娠妇女进行了IL-6、sIL-6 R、sgp 130的检测，其中孕中期39例，孕晚期40例，（n=131，85例IAI阴性和46例IAI阳性）或早产胎膜早破（PPROM：n=91，61例IAI阴性和30例IAI阳性）。采用ELISA、Western blotting和RT-PCR方法检测羊水、胎盘和绒毛组织中sIL-6 R、sgp 130、IL-6 R和gp 130蛋白和mRNA的表达。对组织进行IL-6 R、gp 130、CD 15+（多形性）和CD 3+（T细胞）炎性细胞免疫染色。离体检测sIL-6 R和sgp 130调节绒毛膜基质金属蛋白酶-9（MMP-9）的基础和LPS刺激释放的能力。我们发现，在生理性妊娠中，羊水sgp 130在足月时降低。IAI组羊水IL-6、sIL-6 R升高，PPROM组sgp 130降低。提示羊水中sIL-6 R和sgp 130可能来源于胎膜。免疫组化和RT-PCR显示IAI患者绒毛膜IL-6 R表达增加，gp 130表达减少。离体时，sIL-6 R和LPS增加了绒毛膜MMP-9的释放，而sgp 130则相反。我们的结论是，IL-6的反式信号分子是生理成分的羊水调节胎龄和炎症。PPROM可能涉及sgp 130的功能丧失。
Classic IL-6 signaling is conditioned by the transmembrane receptor (IL-6R) and homodimerization of gp130. During trans-signaling, IL-6 binds to soluble IL-6R (sIL-6R) enabling activation of cells expressing solely gp130. Soluble gp130 (sgp130) selectively inhibits IL-6 trans-signaling. To characterize amniotic fluid IL-6 trans-signaling molecules (IL-6, sIL-6R, sgp130) in normal gestations and pregnancies complicated by intra-amniotic inflammation (IAI) we studied 301 women during second trimester (n=39), third trimester (n=40) and preterm labor with intact (n=131, 85 IAI negative & 46 IAI positive) or preterm premature rupture of membranes (PPROM: n=91, 61 IAI negative & 30 IAI positive). ELISA, Western blotting and RT-PCR were used to investigate amniotic fluid, placenta and amniochorion for protein and mRNA expression of sIL-6R, sgp130, IL-6R and gp130. Tissues were immunostained for IL-6R, gp130, CD15+ (polymorphonuclear) and CD3+ (T-cell) inflammatory cells. The ability of sIL-6R and sgp130 to modulate basal and LPS-stimulated release of amniochorion matrix-metalloprotease-9 (MMP-9) was tested ex-vivo. We showed that in physiologic gestations amniotic fluid sgp130 decreases toward term. Amniotic fluid IL-6 and sIL-6R were elevated in IAI whereas sgp130 was decreased in PPROM. Our results suggested that fetal membranes are the probable source of amniotic fluid sIL-6R and sgp130. Immunohistochemistry and RT-PCR revealed increased IL-6R and decreased gp130 expression in amniochorion of women with IAI. Ex-vivo, sIL-6R and LPS augmented amniochorion MMP-9 release whereas sgp130 opposed this effect. We conclude that IL-6 trans-signaling molecules are physiologic constituents of the amniotic fluid regulated by gestational age and inflammation. PPROM likely involves functional loss of sgp130.
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影响因子：
3.6
作者：
Arechavaleta-Velasco, F;Ogando, D;Vadillo-Ortega, F
通讯作者：
Vadillo-Ortega, F
DOI：
10.1111/j.1471-0528.2004.00340.x
发表时间：
2005-02-01
影响因子：
5.8
作者：
Buhimschi, IA;Christner, R;Buhimschi, CS
通讯作者：
Buhimschi, CS
影响因子：
3.6
作者：
Keelan, JA;Sato, T;Mitchell, MD
通讯作者：
Mitchell, MD
影响因子：
4.6
作者：
Lemmers, A.;Gustot, T.;Deviere, J.
通讯作者：
Deviere, J.
影响因子：
3.3
作者：
Jacques, SM;Qureshi, F
通讯作者：
Qureshi, F