TLR9 provokes inflammation in response to fetal DNA: mechanism for fetal loss in preterm birth and preeclampsia.
نویسندگان
چکیده
Preterm birth, the major cause of neonatal mortality in developed countries, is associated with intrauterine infections and inflammation, although the exact mechanisms underlying this event are unclear. In this study, we show that circulating fetal DNA, which is elevated in pregnancies complicated by preterm labor or preeclampsia, triggers an inflammatory reaction that results in spontaneous preterm birth. Fetal DNA activates NF-κB, shown by IκBα degradation in human PBMCs resulting in production of proinflammatory IL-6. We show that fetal resorption and preterm birth are rapidly induced in mice after i.p. injection of CpG or fetal DNA (300 μg/dam) on gestational day 10-14. In contrast, TLR9(-/-) mice were protected from these effects. Furthermore, this effect was blocked by oral administration of the TLR9 inhibitor chloroquine. Our data therefore provide a novel mechanism for preterm birth and preeclampsia, highlighting TLR9 as a potential therapeutic target for these common disorders of pregnancy.
منابع مشابه
Comment on "TLR9 provokes inflammation in response to fetal DNA: mechanism for fetal loss in preterm birth and preeclampsia".
متن کامل
Preterm Birth and Preeclampsia Fetal DNA: Mechanism for Fetal Loss in TLR9 Provokes Inflammation in Response to
متن کامل
Inm-3: Reduction: Reasons and Consequences
During the recent decades with increasing the use of assisted reproductive techniques including IVF, IUI and ovulation induction, the rate of multiple pregnancies has been increased worldwide. More than 30% of ART pregnancies are twins or higher-order multiple gestations (triplets or greater) a frequency 15- to 20-fold greater than with spontaneous conceptions. Because of the high cost of treat...
متن کاملI-40: Non Invasive Prenatal Genetic Diagnosis;Current Status and The Future
Discovery of cell free fetal DNA in 1997 has deeply changed the outlook of prenatal diagnosis approaches as most of the clinically established screening tests are not sensitive/specific enough while the current practical diagnostic tests are also invasive in their nature. The most common prenatal screening test is routinely practiced for the diagnosis of Down syndrome (DS) which includes a 10% ...
متن کاملEVALUATION OF FREQUENCY OF MATERNAL AND FETAL COMPLICATIONS IN PATIENTS WITH PREECLAMPSIA ADMITTED TO MOTAHHARI HOSPITAL IN URMIA IN 2019
Background & Aims: Preeclampsia is one of the most serious complications of pregnancy. Preeclampsia can lead to dysfunction of various organs such as the liver, kidneys, and brain, leading to maternal and fetal complications. In this study, we intended to examine the various complications that occur in the mother and fetus due to preeclampsia. Materials & Methods: In the present study, the res...
متن کاملذخیره در منابع من
با ذخیره ی این منبع در منابع من، دسترسی به آن را برای استفاده های بعدی آسان تر کنید
برای دانلود متن کامل این مقاله و بیش از 32 میلیون مقاله دیگر ابتدا ثبت نام کنید
ثبت ناماگر عضو سایت هستید لطفا وارد حساب کاربری خود شوید
ورودعنوان ژورنال:
- Journal of immunology
دوره 188 11 شماره
صفحات -
تاریخ انتشار 2012