Effect of TLR3 and TLR7 activation in uterine NK cells from non-obese diabetic (NOD) mice.
Toll-like receptor (TLR)-TLR cross talk is thought to be important in TLR signaling. Herein, we investigated the effect of specific TLR3 and TLR7 agonists, poly (I:C) and R837, individually and in combination, on uterine immune cell function and their subsequent effects on pregnancy outcome. Allogeneic pregnancies in the non-obese diabetic (NOD) mousexC57BL/6 and wild-type BALB/cxC57BL/6 model were used. An additive increase in embryo resorption was observed after induction with both poly (I:C) and R837, and was associated with elevated numbers of both TNF-alpha- and IFN-gamma-producing CD45(+) cells in the uterus. Further examination showed that while cytokine expression was detected in both CD3(+) cells and CD49b(+) cells in BALB/c mice, NOD mouse cells behaved differently. In NOD mice, elevated cytokine expression was attributed to CD3(+) T cells, with no response detected in the CD49b(+) NK cells. The additive effect of combined agonists was partially inhibited by the Jun N-terminal kinase (JNK) mitogen-activated protein kinase (MAPK) inhibitor SP600125 and almost completely abrogated by the extracellular signal-regulated kinase (ERK) MAPK inhibitor PD98059. These results suggest that increased TLR3 and TLR7 signals are transmitted via Th1-type T cells, rather than NK cells, in NOD mice. Furthermore, the ERK MAPK pathway may be critical in TLR3 and TLR7 signaling.
Lin
Yi
Y
Institute of Obstetrics and Gynecology, Department of Obstetrics and Gynecology, Renji Hospital, Shanghai Jiaotong University, PR China. yilinonline@gmail.com
Ren
Lingling
L
Wang
Wenjing
W
Di
Jingfang
J
Zeng
Shan
S
Saito
Shigeru
S
D000634:Aminoquinolines / Q000008:administration & dosage / Q000494:pharmacology*; D000818:Animals; D000873:Anthracenes / Q000494:pharmacology; D015703:Antigens, CD / Q000096:biosynthesis; D003602:Cytotoxicity, Immunologic / Q000187:drug effects; D020964:Embryo Loss / Q000276:immunology / Q000517:prevention & control; D048049:Extracellular Signal-Regulated MAP Kinases / Q000037:antagonists & inhibitors; D005260:Female; D005419:Flavonoids / Q000494:pharmacology; D000077271:Imiquimod; D007371:Interferon-gamma / Q000378:metabolism; D007694:Killer Cells, Natural / Q000187:drug effects / Q000276:immunology / Q000378:metabolism* / Q000473:pathology; D048670:MAP Kinase Kinase 4 / Q000037:antagonists & inhibitors; D020935:MAP Kinase Signaling System / Q000187:drug effects; D008297:Male; D008562:Membrane Glycoproteins / Q000819:agonists*; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D016688:Mice, Inbred NOD; D011070:Poly I-C / Q000008:administration & dosage / Q000494:pharmacology*; D011247:Pregnancy; D013601:T-Lymphocytes / Q000187:drug effects / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D051196:Toll-Like Receptor 3 / Q000819:agonists*; D051199:Toll-Like Receptor 7 / Q000819:agonists*; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism; D014599:Uterus / Q000187:drug effects / Q000473:pathology
D000634:Aminoquinolines; D000873:Anthracenes; D015703:Antigens, CD; D005419:Flavonoids; D008562:Membrane Glycoproteins; C519703:TLR3 protein, mouse; C477038:Tlr7 protein, mouse; D051196:Toll-Like Receptor 3; D051199:Toll-Like Receptor 7; D014409:Tumor Necrosis Factor-alpha; C432165:pyrazolanthrone; D007371:Interferon-gamma; D048049:Extracellular Signal-Regulated MAP Kinases; D048670:MAP Kinase Kinase 4; D011070:Poly I-C; D000077271:Imiquimod; C093973:2-(2-amino-3-methoxyphenyl)-4H-1-benzopyran-4-one