Atypical Protein Kinase C as a Potential Mediator of Tumour Necrosis Factor-α Induced Nuclear factor-κB Signaling in the Placenta Syncytiotrophoblast
Introduction: Systemic inflammation characterized by increased levels of tumour necrosis factor-α (TNF-α) is a hallmark of pregnancy disorders. Nuclear factor-κB (NF-κB) is a master regulator of inflammation, controlling the expression of thousands of genes. NF-κB activation has been observed in complicated pregnancies within the syncytiotrophoblast (ST). The ST is a giant multinucleated cell that forms the surface of the placenta. Upstream regulators controlling NF-κB activation within the ST have not been thoroughly investigated. Thus, we examined the role of atypical protein kinase C (aPKC), which controls NF-κB activation in other cell types, within the ST.
Methods: Primary trophoblasts were isolated from normal term placenta. These cells were treated with 10ng/ml TNF-α with or without aPKC inhibitors for 2 hours. Cells were then fixed and stained for NF-κB DNA binding component (RelA), E-cadherin, and a nuclear marker and imaged by confocal microscopy.
Results: Cells treated with TNF-α showed a significantly greater proportion of ST nuclei positive for RelA compared to control groups. Simultaneous treatment with both aPKC inhibitors and TNF-α decreased NF-κB activation.
Conclusion: Our results indicate that aPKC mediates TNF-α-induced NF-κB signaling within the ST. Since NF-κB is an important regulator of inflammation, studying the mechanisms governing its activation can offer insight into novel and more specific therapeutic targets for the treatment of inflammatory pregnancy disorders. This would ultimately lead to improved maternal and fetal outcomes.