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Objective: We used a mouse model of infection-induced preterm delivery to examine the roles of 2 adaptor proteins with central functions in Toll-like receptor signaling: MyD88 (myeloid differentiation primary-response gene 88) and TRIF (Toll/IL-1 receptor (TIR)-domain-containing adaptor protein-inducing IFN-beta).

Study Design: Mice deficient (KO) for MyD88, TRIF, both (DKO) or neither (WT) were inoculated into the uterus with killed Escherichia coli. Delivery outcomes, fetal status, serum progesterone, and nuclear translocation of the transcription factor nuclear factor kappa B (NFkappaB) were determined.

Results: Preterm birth (delivery in less than 48 hours) occurred in WT and TRIF-KO animals in a dose-dependent fashion, reaching 100% with 5-10 x 10(9) bacteria, while MyD88-KO and DKO animals were completely protected from delivery. Intrauterine fetal survival, maintenance of circulating progesterone levels, and nuclear translocation of NFkappaB were also dependent upon MyD88 but not TRIF. In contrast, induction of uterine interleukin (IL)-1beta and tumor necrosis factor alpha (TNF-alpha) depends upon actions of both MyD88 and TRIF.

Conclusion: E coli-induced preterm delivery in the mouse is completely dependent upon MyD88 but not TRIF.

Titel:	The adaptor protein MyD88 is essential for E coli-induced preterm delivery in mice.
Autor/in / Beteiligte Person:	Filipovich, Y ; Lu, SJ ; Akira, S ; Hirsch, E
Zeitschrift:	American journal of obstetrics and gynecology, Jg. 200 (2009), Heft 1, S. 93.e1-8
Veröffentlichung:	<2005->: New York : Elsevier ; <i>Original Publication</i>: St. Louis., 2009
Medientyp:	academicJournal
ISSN:	1097-6868 (electronic)
DOI:	10.1016/j.ajog.2008.08.038
Schlagwort:	Animals Female Immunohistochemistry Male Mice Mice, Inbred C57BL Mice, Knockout Myeloid Differentiation Factor 88 genetics NF-kappa B metabolism Pregnancy Pregnancy Complications, Infectious microbiology Premature Birth metabolism Progesterone metabolism RNA chemistry RNA genetics Receptors, Interleukin genetics Receptors, Interleukin metabolism Reverse Transcriptase Polymerase Chain Reaction Signal Transduction Statistics, Nonparametric Escherichia coli isolation & purification Escherichia coli Infections complications Myeloid Differentiation Factor 88 metabolism Pregnancy Complications, Infectious metabolism Premature Birth microbiology
Sonstiges:	Nachgewiesen in: MEDLINE Sprachen: English Publication Type: Journal Article; Research Support, Non-U.S. Gov't Language: English [Am J Obstet Gynecol] 2009 Jan; Vol. 200 (1), pp. 93.e1-8. MeSH Terms: Escherichia coli / isolation & purification ; Escherichia coli Infections / complications ; Myeloid Differentiation Factor 88 / metabolism ; Pregnancy Complications, Infectious / metabolism ; Premature Birth / *microbiology ; Animals ; Female ; Immunohistochemistry ; Male ; Mice ; Mice, Inbred C57BL ; Mice, Knockout ; Myeloid Differentiation Factor 88 / genetics ; NF-kappa B / metabolism ; Pregnancy ; Pregnancy Complications, Infectious / microbiology ; Premature Birth / metabolism ; Progesterone / metabolism ; RNA / chemistry ; RNA / genetics ; Receptors, Interleukin / genetics ; Receptors, Interleukin / metabolism ; Reverse Transcriptase Polymerase Chain Reaction ; Signal Transduction ; Statistics, Nonparametric Substance Nomenclature: 0 (Myd88 protein, mouse) ; 0 (Myeloid Differentiation Factor 88) ; 0 (NF-kappa B) ; 0 (Receptors, Interleukin) ; 0 (Ticam2 protein, mouse) ; 4G7DS2Q64Y (Progesterone) ; 63231-63-0 (RNA) Entry Date(s): Date Created: 20090106 Date Completed: 20090203 Latest Revision: 20210810 Update Code: 20240513

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The adaptor protein MyD88 is essential for E coli-induced preterm delivery in mice.