These authors contributed equally to this work.
ORIGINAL ARTICLE: Regulation of Nod1 and Nod2 in First Trimester Trophoblast Cells
Article first published online: 2 MAR 2009
© 2009 John Wiley & Sons A/S
American Journal of Reproductive Immunology
Volume 61, Issue 4, pages 294–302, April 2009
How to Cite
Mulla, M. J., Yu, A. G., Cardenas, I., Guller, S., Panda, B. and Abrahams, V. M. (2009), ORIGINAL ARTICLE: Regulation of Nod1 and Nod2 in First Trimester Trophoblast Cells. American Journal of Reproductive Immunology, 61: 294–302. doi: 10.1111/j.1600-0897.2009.00694.x
- Issue published online: 2 MAR 2009
- Article first published online: 2 MAR 2009
- Submitted November 10, 2008; accepted February 5, 2009.
- Innate immunity;
- Pattern recognition;
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.