Evidence for participation of uterine natural killer cells in the mechanisms responsible for spontaneous preterm labor and delivery

Shaun P. Murphy; Nazeeh N. Hanna; Loren D. Fast; Sunil K. Shaw; Göran Berg; James F. Padbury; Roberto Romero; Surendra Sharma

doi:10.1016/j.ajog.2008.10.043

Evidence for participation of uterine natural killer cells in the mechanisms responsible for spontaneous preterm labor and delivery

Shaun P. Murphy, Nazeeh N. Hanna, Loren D. Fast, Sunil K. Shaw, Göran Berg, James F. Padbury, Roberto Romero, Surendra Sharma

Research output: Contribution to journal › Article › peer-review

Abstract

Objective: The purpose of this study was to determine in a mouse model whether uterine natural killer (uNK) cell cytotoxic activation induces infection/inflammation-associated preterm labor and delivery. Study Design: Wild type or interleukin (IL)-10^-/- mice were injected intraperitoneally with lipopolysaccharide on gestational day 14. Mice were either killed for collection of uteroplacental tissue, spleen, and serum or allowed to deliver. Uteroplacental tissue was used for histology and characterization of uNK cells. Results: Low-dose lipopolysaccharide treatment triggered preterm labor and delivery in IL-10^-/-, but not wild type mice, in a manner independent of progesterone levels. Preterm labor and delivery in IL-10^-/- mice was associated with an increased number and placental infiltration of cytotoxic uNK cells and placental cell death. Depletion of NK cells or tumor necrosis factor (TNF)-α neutralization in these mice restored term delivery. Furthermore, TNF-α neutralization prevented uNK cell infiltration and placental cell apoptosis. Conclusion: The uNK cell-TNF-α-IL-10 axis plays an important role in the genesis of infection/inflammation-induced preterm labor/delivery.

Original language	English (US)
Pages (from-to)	308.e1-308.e9
Journal	American journal of obstetrics and gynecology
Volume	200
Issue number	3
DOIs	https://doi.org/10.1016/j.ajog.2008.10.043
State	Published - Mar 2009
Externally published	Yes

Keywords

cytokines
inflammation
preterm birth
uterine natural killer cells

ASJC Scopus subject areas

Obstetrics and Gynecology

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10.1016/j.ajog.2008.10.043

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title = "Evidence for participation of uterine natural killer cells in the mechanisms responsible for spontaneous preterm labor and delivery",

abstract = "Objective: The purpose of this study was to determine in a mouse model whether uterine natural killer (uNK) cell cytotoxic activation induces infection/inflammation-associated preterm labor and delivery. Study Design: Wild type or interleukin (IL)-10-/- mice were injected intraperitoneally with lipopolysaccharide on gestational day 14. Mice were either killed for collection of uteroplacental tissue, spleen, and serum or allowed to deliver. Uteroplacental tissue was used for histology and characterization of uNK cells. Results: Low-dose lipopolysaccharide treatment triggered preterm labor and delivery in IL-10-/-, but not wild type mice, in a manner independent of progesterone levels. Preterm labor and delivery in IL-10-/- mice was associated with an increased number and placental infiltration of cytotoxic uNK cells and placental cell death. Depletion of NK cells or tumor necrosis factor (TNF)-α neutralization in these mice restored term delivery. Furthermore, TNF-α neutralization prevented uNK cell infiltration and placental cell apoptosis. Conclusion: The uNK cell-TNF-α-IL-10 axis plays an important role in the genesis of infection/inflammation-induced preterm labor/delivery.",

keywords = "cytokines, inflammation, preterm birth, uterine natural killer cells",

author = "Murphy, {Shaun P.} and Hanna, {Nazeeh N.} and Fast, {Loren D.} and Shaw, {Sunil K.} and G{\"o}ran Berg and Padbury, {James F.} and Roberto Romero and Surendra Sharma",

year = "2009",

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doi = "10.1016/j.ajog.2008.10.043",

language = "English (US)",

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T1 - Evidence for participation of uterine natural killer cells in the mechanisms responsible for spontaneous preterm labor and delivery

AU - Murphy, Shaun P.

AU - Hanna, Nazeeh N.

AU - Fast, Loren D.

AU - Shaw, Sunil K.

AU - Berg, Göran

AU - Padbury, James F.

AU - Romero, Roberto

AU - Sharma, Surendra

PY - 2009/3

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N2 - Objective: The purpose of this study was to determine in a mouse model whether uterine natural killer (uNK) cell cytotoxic activation induces infection/inflammation-associated preterm labor and delivery. Study Design: Wild type or interleukin (IL)-10-/- mice were injected intraperitoneally with lipopolysaccharide on gestational day 14. Mice were either killed for collection of uteroplacental tissue, spleen, and serum or allowed to deliver. Uteroplacental tissue was used for histology and characterization of uNK cells. Results: Low-dose lipopolysaccharide treatment triggered preterm labor and delivery in IL-10-/-, but not wild type mice, in a manner independent of progesterone levels. Preterm labor and delivery in IL-10-/- mice was associated with an increased number and placental infiltration of cytotoxic uNK cells and placental cell death. Depletion of NK cells or tumor necrosis factor (TNF)-α neutralization in these mice restored term delivery. Furthermore, TNF-α neutralization prevented uNK cell infiltration and placental cell apoptosis. Conclusion: The uNK cell-TNF-α-IL-10 axis plays an important role in the genesis of infection/inflammation-induced preterm labor/delivery.

AB - Objective: The purpose of this study was to determine in a mouse model whether uterine natural killer (uNK) cell cytotoxic activation induces infection/inflammation-associated preterm labor and delivery. Study Design: Wild type or interleukin (IL)-10-/- mice were injected intraperitoneally with lipopolysaccharide on gestational day 14. Mice were either killed for collection of uteroplacental tissue, spleen, and serum or allowed to deliver. Uteroplacental tissue was used for histology and characterization of uNK cells. Results: Low-dose lipopolysaccharide treatment triggered preterm labor and delivery in IL-10-/-, but not wild type mice, in a manner independent of progesterone levels. Preterm labor and delivery in IL-10-/- mice was associated with an increased number and placental infiltration of cytotoxic uNK cells and placental cell death. Depletion of NK cells or tumor necrosis factor (TNF)-α neutralization in these mice restored term delivery. Furthermore, TNF-α neutralization prevented uNK cell infiltration and placental cell apoptosis. Conclusion: The uNK cell-TNF-α-IL-10 axis plays an important role in the genesis of infection/inflammation-induced preterm labor/delivery.

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Evidence for participation of uterine natural killer cells in the mechanisms responsible for spontaneous preterm labor and delivery

Abstract

Keywords

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