The role of c-jun n-terminal kinase (JNK) and tumour protein (p53) in HIV associated pre-eclampsia.

Abstract

Background: In pre-eclampsia, immune maladaptation to the foetal allograft results in impaired trophoblast invasion and defective spiral arterial remodelling with consequential placental oxidative stress. Placental apoptosis can be initiated by various stimuli including hypoxia and oxidative stress and is notably exaggerated in pre-eclampsia. This elevated apoptosis prevents normal replenishment of the syncytiotrophoblast, promotes syncytial degeneration and releases vasoactive or inflammatory factors into the maternal circulation thereby provoking the endothelial dysfunction seen in pre-eclampsia. Since the p53 antigen and JNK are important mediators of apoptosis we determined their expression in HIV associated pre-eclampsia. Method: Blood samples were collected from normotensive pregnant and pre-eclamptic HIV infected and negative women. Buffy coat was extracted and a Bio-plex multiplex assay to quantify expression of phosphorylated-p53 and JNK. Results: Based on pregnancy type, a significant difference in the expression of p53 was noted between the pre-eclamptic vs normotensive pregnant group regardless of HIV status (p=0.0162). Irrespective of pregnancy type, there was also a significant difference found between the HIV positive and HIV negative groups (p=0.0469). Furthermore, there was a significant difference in the expression of p53 between the HIV negative pre-eclamptic vs the HIV negative normotensive group and HIV infected normotensive vs the HIV negative pre-eclamptic group. Despite having no statistical significance (p=0.8701), the expression of JNK was found to be increased in the pre-eclamptic compared to the normotensive pregnant group. Similarly, based on HIV status, regardless of pregnancy type no statistical significance was found (p=0.2227), however, there was a decrease in the expression of JNK in the HIV positive compared to the HIV negative group. xiii Conclusion: These experiments demonstrate a significant increase in the expression of p53 with an upwards trend in the expression of JNK in pre-eclampsia, confirming their influence on trophoblast cell invasion in pre-eclampsia development. This increase in expression of p53 and JNK in pre-eclampsia, holds potential value as a risk indicator of pre-eclamptic development. In contrast, a significant down regulation of p53 with a downwards trend of JNK expression was noted in the HIV positive group, possibly due to immune reconstitution following HAART.