Regulation of Nod1 and Nod2 in first trimester trophoblast cells

Melissa J. Mulla, Andrew G. Yu, Ingrid Cardenas, Seth Guller, Britta Panda, Vikki M. Abrahams

Research output: Contribution to journalArticle

28 Citations (Scopus)

Abstract

Problem: The cytoplasmic pattern recognition receptors, Nod1 and Nod2, are thought to be important for detecting intracellular bacteria. We have previously reported that first trimester trophoblast cells express Nod1 and Nod2, and that trophoblast Nod2 activation triggers an inflammatory response. The objectives of this study were to characterize the effects of Nod1 stimulation, and to determine the regulation of Nod1 and Nod2, in the trophoblast. Method of Study: The effect of Nod1 activation on trophoblast cells was determined by analyzing the cytokine response following treatment with γ-D-glutamyl- meso -diaminopimelic acid (iE-DAP). The regulation of Nod1 and Nod2 expression by trophoblast cells was evaluated by RT-PCR. Results: Treatment of trophoblast cells with iE-DAP significantly increased their production of cytokines and chemokines. In addition, Nod1 and Nod2 mRNA expression was upregulated following treatment of trophoblast cells with lipopolysaccharide (LPS), and this was significantly reduced by the presence of a NFκB inhibitor and a TLR4-dominant negative (DN). Conclusion: This study demonstrates that LPS, through TLR4, increases trophoblast expression of Nod1 and Nod2 via the NFκB pathway; and that Nod1 is functional in the trophoblast. These findings suggest that extracellular recognition of bacterial LPS by TLR4 may prime the trophoblast in preparation for its cytoplasmic recognition of, and response to, bacterial peptides through the Nod proteins.

Original languageEnglish (US)
Pages (from-to)294-302
Number of pages9
JournalAmerican Journal of Reproductive Immunology
Volume61
Issue number4
DOIs
StatePublished - Mar 19 2009
Externally publishedYes

Fingerprint

Trophoblasts
First Pregnancy Trimester
Lipopolysaccharides
Diaminopimelic Acid
Cytokines
Pattern Recognition Receptors
Chemokines
Bacteria
Polymerase Chain Reaction
Messenger RNA
Peptides

Keywords

  • Infection
  • Innate immunity
  • Pattern recognition
  • Placenta
  • Pregnancy

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology
  • Reproductive Medicine
  • Obstetrics and Gynecology

Cite this

Regulation of Nod1 and Nod2 in first trimester trophoblast cells. / Mulla, Melissa J.; Yu, Andrew G.; Cardenas, Ingrid; Guller, Seth; Panda, Britta; Abrahams, Vikki M.

In: American Journal of Reproductive Immunology, Vol. 61, No. 4, 19.03.2009, p. 294-302.

Research output: Contribution to journalArticle

Mulla, Melissa J. ; Yu, Andrew G. ; Cardenas, Ingrid ; Guller, Seth ; Panda, Britta ; Abrahams, Vikki M. / Regulation of Nod1 and Nod2 in first trimester trophoblast cells. In: American Journal of Reproductive Immunology. 2009 ; Vol. 61, No. 4. pp. 294-302.
@article{38ef6675e4734cbea72fba484d18ec35,
title = "Regulation of Nod1 and Nod2 in first trimester trophoblast cells",
abstract = "Problem: The cytoplasmic pattern recognition receptors, Nod1 and Nod2, are thought to be important for detecting intracellular bacteria. We have previously reported that first trimester trophoblast cells express Nod1 and Nod2, and that trophoblast Nod2 activation triggers an inflammatory response. The objectives of this study were to characterize the effects of Nod1 stimulation, and to determine the regulation of Nod1 and Nod2, in the trophoblast. Method of Study: The effect of Nod1 activation on trophoblast cells was determined by analyzing the cytokine response following treatment with γ-D-glutamyl- meso -diaminopimelic acid (iE-DAP). The regulation of Nod1 and Nod2 expression by trophoblast cells was evaluated by RT-PCR. Results: Treatment of trophoblast cells with iE-DAP significantly increased their production of cytokines and chemokines. In addition, Nod1 and Nod2 mRNA expression was upregulated following treatment of trophoblast cells with lipopolysaccharide (LPS), and this was significantly reduced by the presence of a NFκB inhibitor and a TLR4-dominant negative (DN). Conclusion: This study demonstrates that LPS, through TLR4, increases trophoblast expression of Nod1 and Nod2 via the NFκB pathway; and that Nod1 is functional in the trophoblast. These findings suggest that extracellular recognition of bacterial LPS by TLR4 may prime the trophoblast in preparation for its cytoplasmic recognition of, and response to, bacterial peptides through the Nod proteins.",
keywords = "Infection, Innate immunity, Pattern recognition, Placenta, Pregnancy",
author = "Mulla, {Melissa J.} and Yu, {Andrew G.} and Ingrid Cardenas and Seth Guller and Britta Panda and Abrahams, {Vikki M.}",
year = "2009",
month = "3",
day = "19",
doi = "10.1111/j.1600-0897.2009.00694.x",
language = "English (US)",
volume = "61",
pages = "294--302",
journal = "American Journal of Reproductive Immunology",
issn = "8755-8920",
publisher = "Wiley-Blackwell",
number = "4",

}

TY - JOUR

T1 - Regulation of Nod1 and Nod2 in first trimester trophoblast cells

AU - Mulla, Melissa J.

AU - Yu, Andrew G.

AU - Cardenas, Ingrid

AU - Guller, Seth

AU - Panda, Britta

AU - Abrahams, Vikki M.

PY - 2009/3/19

Y1 - 2009/3/19

N2 - Problem: The cytoplasmic pattern recognition receptors, Nod1 and Nod2, are thought to be important for detecting intracellular bacteria. We have previously reported that first trimester trophoblast cells express Nod1 and Nod2, and that trophoblast Nod2 activation triggers an inflammatory response. The objectives of this study were to characterize the effects of Nod1 stimulation, and to determine the regulation of Nod1 and Nod2, in the trophoblast. Method of Study: The effect of Nod1 activation on trophoblast cells was determined by analyzing the cytokine response following treatment with γ-D-glutamyl- meso -diaminopimelic acid (iE-DAP). The regulation of Nod1 and Nod2 expression by trophoblast cells was evaluated by RT-PCR. Results: Treatment of trophoblast cells with iE-DAP significantly increased their production of cytokines and chemokines. In addition, Nod1 and Nod2 mRNA expression was upregulated following treatment of trophoblast cells with lipopolysaccharide (LPS), and this was significantly reduced by the presence of a NFκB inhibitor and a TLR4-dominant negative (DN). Conclusion: This study demonstrates that LPS, through TLR4, increases trophoblast expression of Nod1 and Nod2 via the NFκB pathway; and that Nod1 is functional in the trophoblast. These findings suggest that extracellular recognition of bacterial LPS by TLR4 may prime the trophoblast in preparation for its cytoplasmic recognition of, and response to, bacterial peptides through the Nod proteins.

AB - Problem: The cytoplasmic pattern recognition receptors, Nod1 and Nod2, are thought to be important for detecting intracellular bacteria. We have previously reported that first trimester trophoblast cells express Nod1 and Nod2, and that trophoblast Nod2 activation triggers an inflammatory response. The objectives of this study were to characterize the effects of Nod1 stimulation, and to determine the regulation of Nod1 and Nod2, in the trophoblast. Method of Study: The effect of Nod1 activation on trophoblast cells was determined by analyzing the cytokine response following treatment with γ-D-glutamyl- meso -diaminopimelic acid (iE-DAP). The regulation of Nod1 and Nod2 expression by trophoblast cells was evaluated by RT-PCR. Results: Treatment of trophoblast cells with iE-DAP significantly increased their production of cytokines and chemokines. In addition, Nod1 and Nod2 mRNA expression was upregulated following treatment of trophoblast cells with lipopolysaccharide (LPS), and this was significantly reduced by the presence of a NFκB inhibitor and a TLR4-dominant negative (DN). Conclusion: This study demonstrates that LPS, through TLR4, increases trophoblast expression of Nod1 and Nod2 via the NFκB pathway; and that Nod1 is functional in the trophoblast. These findings suggest that extracellular recognition of bacterial LPS by TLR4 may prime the trophoblast in preparation for its cytoplasmic recognition of, and response to, bacterial peptides through the Nod proteins.

KW - Infection

KW - Innate immunity

KW - Pattern recognition

KW - Placenta

KW - Pregnancy

UR - http://www.scopus.com/inward/record.url?scp=62249121764&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=62249121764&partnerID=8YFLogxK

U2 - 10.1111/j.1600-0897.2009.00694.x

DO - 10.1111/j.1600-0897.2009.00694.x

M3 - Article

C2 - 19260860

AN - SCOPUS:62249121764

VL - 61

SP - 294

EP - 302

JO - American Journal of Reproductive Immunology

JF - American Journal of Reproductive Immunology

SN - 8755-8920

IS - 4

ER -