Brianna Lyttle1, Jinghua Chai, Juan M Gonzalez, Hua Xu, Mary Sammel, Michal A Elovitz. 1. Maternal and Child Health Research Program, Department of Obstetrics and Gynecology, Center for Research on Reproduction and Women's Health, University of Pennsylvania Medical Center, Philadelphia, PA, USA.
Abstract
OBJECTIVE: Toll-like receptors (TLRs) are essential mediators of host immunity. TLR activation must be tightly regulated to prevent an exaggerated immune response from devastating the host. These studies assessed the expression of negative regulators (interleukin receptor-associated kinase [IRAK]-3, IRAK-1, Fas-associated protein with death domain) during pregnancy and in preterm birth (PTB). STUDY DESIGN: Tissues (uterine, cervix, placenta, and spleens) from the following experimental groups were harvested: (1) nonpregnant mice, (2) pregnant mice across gestation, (3) murine model of PTB, and (4) pregnant mice exposed to medroxyprogesterone acetate (MPA). RESULTS: Negative regulators are differentially expressed in the uterus during pregnancy. In the setting of PTB, IRAK-3 is significantly increased in the uterus and cervix but not the placenta. In maternal spleens, IRAK-3 and IRAK-1 are increased in response to intrauterine inflammation. MPA can increase IRAK expression in cervical tissues. CONCLUSION: Negative regulators of the maternal immune response may play an important role in protecting pregnancies from an exaggerated inflammatory response.
OBJECTIVE: Toll-like receptors (TLRs) are essential mediators of host immunity. TLR activation must be tightly regulated to prevent an exaggerated immune response from devastating the host. These studies assessed the expression of negative regulators (interleukin receptor-associated kinase [IRAK]-3, IRAK-1, Fas-associated protein with death domain) during pregnancy and in preterm birth (PTB). STUDY DESIGN: Tissues (uterine, cervix, placenta, and spleens) from the following experimental groups were harvested: (1) nonpregnant mice, (2) pregnant mice across gestation, (3) murine model of PTB, and (4) pregnant mice exposed to medroxyprogesterone acetate (MPA). RESULTS: Negative regulators are differentially expressed in the uterus during pregnancy. In the setting of PTB, IRAK-3 is significantly increased in the uterus and cervix but not the placenta. In maternal spleens, IRAK-3 and IRAK-1 are increased in response to intrauterine inflammation. MPA can increase IRAK expression in cervical tissues. CONCLUSION: Negative regulators of the maternal immune response may play an important role in protecting pregnancies from an exaggerated inflammatory response.
Authors: Koichi Kobayashi; Lorraine D Hernandez; Jorge E Galán; Charles A Janeway; Ruslan Medzhitov; Richard A Flavell Journal: Cell Date: 2002-07-26 Impact factor: 41.582
Authors: Pamela L Follett; Wenbin Deng; Weimin Dai; Delia M Talos; Leon J Massillon; Paul A Rosenberg; Joseph J Volpe; Frances E Jensen Journal: J Neurosci Date: 2004-05-05 Impact factor: 6.167
Authors: Hakim Echchannaoui; Karl Frei; Christian Schnell; Stephen L Leib; Werner Zimmerli; Regine Landmann Journal: J Infect Dis Date: 2002-08-16 Impact factor: 5.226
Authors: Paul J Meis; Mark Klebanoff; Elizabeth Thom; Mitchell P Dombrowski; Baha Sibai; Atef H Moawad; Catherine Y Spong; John C Hauth; Menachem Miodovnik; Michael W Varner; Kenneth J Leveno; Steve N Caritis; Jay D Iams; Ronald J Wapner; Deborah Conway; Mary J O'Sullivan; Marshall Carpenter; Brian Mercer; Susan M Ramin; John M Thorp; Alan M Peaceman; Steven Gabbe Journal: N Engl J Med Date: 2003-06-12 Impact factor: 91.245