Regeneration and tolerance factor of the human placenta induces IL-10 production

Abstract

Regeneration and tolerance factor (RTF) was originally identified in the placenta of mice and the isolated protein shown to have suppressive effects. In these studies, the gene cloned from thymus tissue was mapped to human chromosome 12. The role of recombinant RTF on cytokines was examined. In addition, we examined the human placenta by immunohistochemistry for RTF expression. RTF was expressed at the peripheral layer of cytotrophoblast in 7–9‐week‐old placentas. Using the RTF gene sequence, a recombinant protein was prepared and shown to induce IL‐10 production. These data indicate that RTF is expressed by the tissues most intimately involved at the maternal‐fetal interface, and its biological activity is capable of producing the necessary immune response for initiating and maintaining the maternal‐fetal relationship.

Vacuolar-ATPase (V-ATPase) Mediates Progesterone-Induced Uterine Fluid Acidification in Rats

“…V-ATPase A2 was highly expressed in the pre-implantation embryos (Jaiswal et al 2012). Embryo V-ATPase A2 was involved in the regulation of maternal immune responses that is crucial for the pregnancy establishment (Jaiswal et al 2011;Lee et al 2001). In addition, V-ATPase A2 also regulates the cytokine and chemokine networks that coordinate macrophage recruitment to the feto-maternal interface for placental growth and development (Jaiswal et al 2011).…”

Novel role for the N-terminus domain of the a2 isoform of vacuolar ATPase in interleukin-1β production

“…It was shown that a2V-ATPase could modulate IL-1␤ secretion from a human macrophage cell line [15]. Furthermore, it has been found that the N-terminus domain of the a2V-ATPase caused an increase in IL-10 production and a considerable reduction in IL-2 production from stimulated T cells [9]. In addition, the N-terminus domain of the a2V-ATPase is expressed in cycling and pregnant endometrium and IL-1␤ increases its mRNA expression [16].…”

“…Because of the first identification of a2NTD as a major protein in the maintenance of pregnancy, its early effects were targeted to Th2 cytokines, such as IL-10 [9]. The current research was conducted to investigate the role of a2NTD in cytokine secretion.…”

“…a2V-ATPase has a role in pregnancy [9] and tumorigenesis [10]. Upon cell activation, a2V-ATPase translocates to the plasma membrane, where it resides as a 50-kDa molecule.…”

“…Upon cell activation, a2V-ATPase translocates to the plasma membrane, where it resides as a 50-kDa molecule. The remaining hydrophilic external 20 kDa N-terminus domain is proteolytically cleaved and is found in the extracellular environment [9,11].…”