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

Lee, Gerald W; Boomer, Jonathan S.; Gilman‐Sachs, Alice; Chedid, Antonio; Gudelj, Lea; Rukavina, Daniel; Beaman, Kenneth D.

doi:10.1002/1521-4141(200103)31:3<687::aid-immu687>3.3.co;2-9

Cited by 9 publications

(9 citation statements)

References 8 publications

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“…Earlier studies associated a number of immunological effects with a2V expression (20,21) as well as with the recombinantly expressed peptide (10). In similar experiments, MDA cocultured with PBMCs induced the most IL-1b compared with the other cell lines; this correlated with the relatively high a2V expression in MDA cells (Fig.…”

Section: A2v-atpase Utilizes Microvesicles In Il-1b Inductionmentioning

confidence: 99%

Tumor-Associated a2 Vacuolar ATPase Acts As a Key Mediator of Cancer-Related Inflammation by Inducing Pro-Tumorigenic Properties in Monocytes

Kwong

Gilman‐Sachs

Beaman

2011

The Journal of Immunology

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Cancer-related inflammation profoundly affects tumor progression. Tumor-associated macrophages (TAMs) are known regulators of that inflammation, but the factors that initiate cancer-related inflammation are poorly understood. Tumor invasiveness and poor clinical outcome are linked to increased expression of cell surface-associated vacuolar adenosine triphosphatases. The a2 isoform vacuolar adenosine triphosphatase is found on the surface on many solid tumors, and we have identified a peptide cleaved from a2 isoform vacuolar adenosine triphosphatase called a2NTD. a2NTD has properties necessary to induce monocytes into a pro-oncogenic TAM phenotype. The peptide upregulated both pro- and anti-inflammatory mediators. These included IL-1β and IL-10, which are important in promoting inflammation and immune escape by tumor cells. The secretion of inflammatory cytokine IL-1β was dependent on ATP, K+ efflux, and reactive oxygen species, all mediators that activate the inflammasome. These findings describe a mechanism by which tumor cells affect the maturation of TAMs via a nontraditional cytokine-like signal, the a2NTD peptide.

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Section: A2v-atpase Utilizes Microvesicles In Il-1b Inductionmentioning

confidence: 99%

Tumor-Associated a2 Vacuolar ATPase Acts As a Key Mediator of Cancer-Related Inflammation by Inducing Pro-Tumorigenic Properties in Monocytes

Kwong

Gilman‐Sachs

Beaman

2011

The Journal of Immunology

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“…We tested mouse sperm for the presence of an important immune regulatory molecule a2V and studied its possible immune-regulatory role during capacitation and early embryonic development. Earlier studies demonstrated that a2V is one of the first molecules expressed in pregnancy that has regulatory effects on the maternal immune response (Lee et al 2001). Sun-Wada et al (2002) have previously reported that a2V was expressed in mature sperm.…”

Section: Introductionmentioning

confidence: 99%

V-ATPase upregulation during early pregnancy: a possible link to establishment of an inflammatory response during preimplantation period of pregnancy

Jaiswal¹,

Mallers²,

Larsen³

et al. 2012

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104

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Various mechanisms exist to prevent a potentially deleterious maternal immune response that results in compromising survival of semiallogeneic fetus. In pregnancy, there is a necessary early preimplantation inflammatory stage followed by a postimplantation antiinflammatory stage. Thus, there is a biphasic 'immune response' observed during the course of pregnancy. We provide the evidence that capacitation of sperm induced the expression of a2 isoform of V-ATPase (ATP6V0A2 referred to as a2V), leukemia inhibitory factor (Lif), Il1b, and Tnf in the sperm. Capacitated sperm also released cleaved N-terminal domain of a2V-ATPase (a2NTD), which upregulates the gene expression of Lif, Il1b, Tnf, and monocyte chemotactic protein-1 (Ccl2 (Mcp1)) in the uterus. Unfertilized eggs had low a2V expression, but after fertilization, the expression of a2V increased in zygotes. This increased level of a2V expression was maintained in preimplantation embryos. Seminal plasma was necessary for upregulation of a2V expression in preimplantation embryos, as mating with seminal vesicle-deficient males failed to elicit an increase in a2V expression in preimplantation embryos. The infiltration of macrophages into the uterus was significantly increased after insemination of both sperm and seminal plasma during the preimplantation period of pregnancy. This dynamic infiltration into the uterus corresponded with the uterine a2V expression through the induction of Ccl2 expression. Furthermore, the polarization ratio of M1:M2 (pro-inflammatory/anti-inflammatory) macrophages in the uterus fluctuated from a ratio of 1.60 (day 1) to 1.45 (day 4) when female mice were inseminated with both sperm and seminal plasma. These data provide evidence that exposure to semen may initiate an inflammatory milieu by inducing a2V and cytokine/chemokine expression, which triggers the influx of macrophages into the preimplantation uterus during the onset of pregnancy and ultimately leads to successful pregnancy outcome.

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“…There are already known examples of proteins like the regeneration and tolerance factor (RTF) or the oncofoetal protein 5T4 that are expressed in pregnancy tissues as well as in malignantly transformed cells. [7][8][9][10] RTF, similarly to secreted PIBF, exerts an immunosuppressive activity and is expressed during pregnancy by the placenta. 7 Here we present evidence that tumor cells overexpress PIBF relative to normal tissues.…”

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confidence: 99%

“…[7][8][9][10] RTF, similarly to secreted PIBF, exerts an immunosuppressive activity and is expressed during pregnancy by the placenta. 7 Here we present evidence that tumor cells overexpress PIBF relative to normal tissues. We also demonstrate that different forms of the molecule are generated by alternative mRNA splicing both in normal and malignant cells.…”

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PIBF (progesterone induced blocking factor) is overexpressed in highly proliferating cells and associated with the centrosome

Lachmann

Gelbmann

Kálmán

et al. 2004

Intl Journal of Cancer

103

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PIBF was previously identified as a 34 kDa immunomodulatory molecule secreted by pregnancy lymphocytes and is thought to play a crucial role in preventing rejection of the embryo by the maternal immune response. Recent data suggested that PIBF protein was also expressed by the progesterone receptor (PR) positive MCF-7 breast tumor cell line. Given the notion that a number of proteins shown to be involved in tumorigenesis are associated with the centrosome and disturbed centrosome function causes unequal segregation of chromosomes, studies to evaluate whether or not PIBF that is highly expressed in tumors is directly involved in tumorigenesis are thus warranted.

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

Cited by 9 publications

References 8 publications

Tumor-Associated a2 Vacuolar ATPase Acts As a Key Mediator of Cancer-Related Inflammation by Inducing Pro-Tumorigenic Properties in Monocytes

Tumor-Associated a2 Vacuolar ATPase Acts As a Key Mediator of Cancer-Related Inflammation by Inducing Pro-Tumorigenic Properties in Monocytes

V-ATPase upregulation during early pregnancy: a possible link to establishment of an inflammatory response during preimplantation period of pregnancy

PIBF (progesterone induced blocking factor) is overexpressed in highly proliferating cells and associated with the centrosome

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