Contribution of vasoactive intestinal peptide to immune homeostasis in trophoblast-maternal leukocyte interaction under LPS stimulation.

BACKGROUND/AIMS: The maternal-fetal interface is a unique immunological site that generates an adequate microenvironment during pregnancy, recognizing and eliminating infections and tolerating the trophoblast/placenta unit. For that purpose, trophoblast cells display several tolerogenic mechanisms to allow fetal survival, such as production of the neuropeptide vasoactive intestinal peptide (VIP). Here we investigated the contribution of VIP to maintain homeostasis at the maternal-placental interface under lipopolysaccharide (LPS) stimulation. METHODS: We performed cocultures between trophoblast cells (Swan-71 cell line) and maternal leukocytes obtained from fertile women as an in vitro model of maternal-placental interaction, and we focused on the effects of LPS on the modulation of VIP and their receptors (VPAC1 and VPAC2). RESULTS: VIP could prevent the upregulation of IL-6, MCP-1, and nitrite production and maintain the production of IL-10 and TGF-ß under LPS (10 µg/ml) stimulation after 48 h of coculture. To gain deeper insight into the mechanisms of how VIP could contribute to a tolerogenic microenvironment even in the presence of LPS, we investigated VIP production by maternal leukocytes and observed a significant increase in the frequency of CD4+VIP+ cells after interaction with Swan-71 cells in the presence of LPS. LPS increased VIP and inducible receptor VPAC2 expression directly on trophoblast cells in a dose- and time-dependent manner. CONCLUSIONS: The present results suggest that VIP might act as an additional homeostatic mechanism during early stages at the maternal-placental interface to control exacerbated inflammatory responses such as the ones observed in intrauterine infections.

Modulation of maternal LIF producers T cells by trophoblast and paternal antigens.

PROBLEM: Fetal implantation enhances the production of essential growth factors such as LIF (leukaemia inhibitory factor), hence we investigated the contribution of maternal CD4 cells, activated by paternal or trophoblast antigens and its modulation by VIP (vasoactive intestinal peptide) and progesterone. METHOD OF STUDY: We performed co cultures of trophoblast cells (Swan-71 cell line) or paternal antigens and PBMCs from patients with recurrent spontaneous abortions (RSA) and fertile women. RESULT: Fertile-CD4(+) LIF(+) cells were increased by VIP and progesterone in response to paternal and trophoblast antigens. Also MMP-9 activity was decreased and pSTAT3/STAT3 ratio was increased. RSA patients have decreased levels of LIF expression which could not be modulated by VIP and progesterone and displayed a reduced number of endometrial infiltrated CD4(+) LIF(+) cells compared with fertile women. CONCLUSION: The decrease of CD4(+) LIF(+) cells in RSA patients could be related with the exacerbated inflammatory response observed in the maternal-fetal dialogue model.

Níveles plasmáticos de un marcador de peroxidación lipídica y de vitamina E en mujeres sanas eumenorreicas, en postmenopáusicas sanas y en primigestas que desarrollaron o no hipertensión inducida / Even plasmatic od a marker of lipid peroxidation and E vitamin in women healthy eumenorreicas, in health postmenopausal and in primigravidas that develope or not induced hypertension

Modificaciones en níveles circulantes de malondialdehido y de vitamina E se han asociaado con hipertensión inducida por embarazo, con diabetes gestacional y con parto pretérmino. Hay solo información fragmentaria aa esstos respectos