Interferon-γ and tumor necrosis factor-α sensitize primarily resistant human endometrial stromal cells to Fas-mediated apoptosis

Fluhr, Herbert; Krenzer, Stefanie; Stein, Gerburg M.; Stork, Björn; Deperschmidt, M.; Wallwiener, D.; Wesselborg, Sebastian; Zygmunt, Marek; Licht, Peter B.

doi:10.1242/jcs.009761

Cited by 52 publications

(34 citation statements)

References 39 publications

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“…As shown in Table 2, compared with the proliferating counterpart, senescent cells showed increased secretion of several cytokines and chemokines. In line with a gradual development of Among cytokines, TNF-a and IFN-g have been show to synergistically induce Fas expression in stromal endometrial cells (Fluhr et al, 2007). In agreement with these data, combined treatment with TNF-a and IFN-g, readily upregulated surface Fas on proliferating A549 cells (Figure 5a), and proliferating MCF-7 cells ( Figure 5b).…”

Section: Sasp Mediates Fas Upregulationsupporting

confidence: 81%

“…Senescent cells secrete cytokines and other factors that affect senescent cells, as well as neighboring cells, via autocrine/paracrine signaling (Freund et al, 2010). As inflammatory cytokines induce Fas expression in different cell types (Kimura et al, 2003;Fluhr et al, 2007), we wondered whether upregulation of Fas in senescent tumor cells was dependent on SASP. To identify secreted factors produced by premature senescent tumor cells, we measured cytokine/chemokine in conditioned media from proliferating and senescent MCF-7 cells, using a 30-plex cytokine assay.…”

Section: Sasp Mediates Fas Upregulationmentioning

confidence: 99%

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NF-κB-dependent cytokine secretion controls Fas expression on chemotherapy-induced premature senescent tumor cells

et al. 2011

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Induction of a senescent phenotype in tumor cells has been linked to anticancer immune response, however, the molecular mechanisms mediating these phenomenon have not yet been determined. In this study, we present evidence that induction of premature senescence in human cancer cell lines induces Fas expression, and loss of resistance to Fas-induced apoptosis. Triggering of Fas by using the agonistic antibody CH11 or the recombinant ligand APO010, activates an apoptotic pathway responsible for cell death. Secretion of pro-inflammatory cytokines by the senescent cells, particularly TNF-a and IFN-c, mediates Fas upregulation. Indeed, treatment of proliferating cancer cell lines with TNF-a and IFN-c, upregulates Fas expression, while blocking TNF-a and IFN-c by using neutralizing antibodies, decreases Fas expression in senescent cells. We also demonstrate that NF-jB has a central role in controlling the senescence-associated secretory phenotype (SASP) by the premature senescent cells, and that TNF-a and IFN-c, transcriptionally controlled by NF-jB, are the main mediators of Fas upregulation. Our data suggest the existence of an NF-jB-dependent autocrine loop, mediated by TNF-a and IFN-c, responsible for expression of Fas on the surface of senescent cells, and for their killing.

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Section: Sasp Mediates Fas Upregulationsupporting

confidence: 81%

Section: Sasp Mediates Fas Upregulationmentioning

confidence: 99%

NF-κB-dependent cytokine secretion controls Fas expression on chemotherapy-induced premature senescent tumor cells

et al. 2011

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“…33 IFN-␥ has been reported to enhance the GVL activity of donor T cells and is also involved in limiting GVHD activities by increasing apoptosis of CD4 ϩ and CD8 ϩ T cells, regulating target gene expression, modulating the susceptibility of GVHD target tissues to damage by alloreactive T cells, [32][33][34][35] and inducing IDO gene expression. 26,27,36 Our data support a critical role for IFN-␥ synthesis by donor T cells and IDO up-regulation by donor pDCs in limiting donor T-cell expansion and GVHD.…”

Section: Discussionmentioning

confidence: 99%

IFN-γ and indoleamine 2,3-dioxygenase signaling between donor dendritic cells and T cells regulates graft versus host and graft versus leukemia activity

Giver

Sharma

et al. 2012

Blood

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IntroductionDonor T cells are responsible for both GVHD and GVL reactions after allogeneic HSCT. The activation status of T cells is modulated by dendritic cells (DCs), the most potent and professional antigenpresenting cells (APCs). 1,2 Both host and donor DCs have been shown to play critical roles in regulating GVHD and GVL effects after MHC-mismatched HSCT. 3-7 GVHD can be initiated by residual APCs that directly present host antigen (Ag) to donor T cells, 5 whereas GVHD intensity can be modulated by donor APCs that present host Ag to donor T cells via indirect antigen presentation. 1,3,8 However, despite extensive investigations of the role of host DCs on GVHD pathophysiology, much less is known about the mechanisms by which donor APCs activate and regulate donor T cells. A previous study by MacDonald et al 9 demonstrated that depleting CD11c ϩ donor conventional DCs (CDCs) reduced the severity of GVHD in mice. The same group then demonstrated that conventional donor cDCs isolated from the spleen are the most effective population in presenting alloantigen and stimulating naive donor T-cell responses early post-bone marrow transplantation (BMT). 3 Recently, using 2 allogeneic murine BMT models (C57BL/ 63B10.BR and C3H3C57BL/6), we showed that addition of donor bone marrow cells enriched for pre-pDCs to a graft composed of purified HSC and T cells significantly improved long-term leukemia-free survival without increasing GVHD compared with recipients of donor HSC and T cells. 10 Of note, higher numbers of IFN-␥-producing donor T cells were seen among recipients of pDCs. 10 The aim of the present work was to further define the mechanism by which donor pre-pDCs modulate the alloreactivity of donor T cells. Based on the marked up-regulation of IFN-␥ in donor T cells cotransplanted with bone marrow enriched for pre-pDCs, 10,11 we hypothesized that IFN-␥-responsive genes in donor pre-pDCs might be involved in their immunomodulatory activity.Using highly purified populations of donor pre-pDCs, we observed that IFN-␥ signaling by donor T cells to donor pre-pDCs led to increased indoleamine-2,3-dioxygenase (IDO) expression in donor pDCs and that IDO production by donor pDCs suppressed the GVHD activity of donor T cells and changed the balance between regulatory and inflammatory donor T cells. These data support a new paradigm for immune regulation in allogeneic HSCT in which donor DCs first activate donor T cells and then subsequently limit GVHD through IDO-dependent modulation of inflammation. Methods Mice B10.BR (H-2K k ), C57BL/6 (B6, H-2K b ), and FVB (H-2K q ) mice, as well as congenic strains of B6 expressing CD45.1 or CD90.1, and IFN-␥, IFN-␥ receptor, and IDO1 knockout strains on the B6 background (IFN-␥ Ϫ/Ϫ , IFNGR1 Ϫ/Ϫ , and IDO1 Ϫ/Ϫ ), were purchased from The Jackson Laboratory. A congenic strain of B10.BR (H-2K k ) expressing CD90.1, named BA.B10, For personal use only. on May 10, 2018. by guest www.bloodjournal.org From was generated by crossing B6 CD90.1 and B10.BR mice and then backcrossing 10 generatio...

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“…Despite the necessity of a dominant pro-inflammatory profile for early pregnancy success [104], heightened inflammatory activation would interfere with normal trophoblast invasion [103]. This was shown by in vitro experiments in which cytokines were observed to inhibit trophoblast invasion [105,106].…”

Section: Sleepmentioning

confidence: 99%

Mechanisms underlying the effects of prenatal psychosocial stress on child outcomes: beyond the HPA axis

Beijers

Buitelaar²,

Weerth

2014

Eur Child Adolesc Psychiatry

283

275

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Accumulating evidence from preclinical and clinical studies indicates that maternal psychosocial stress and anxiety during pregnancy adversely affect child outcomes. However, knowledge on the possible mechanisms underlying these relations is limited. In the present paper, we review the most often proposed mechanism, namely that involving the HPA axis and cortisol, as well as other less well-studied but possibly relevant and complementary mechanisms. We present evidence for a role of the following mechanisms: compromised placental functioning, including the 11β-HSD2 enzyme, increased catecholamines, compromised maternal immune system and intestinal microbiota, and altered health behaviors including eating, sleep, and exercise. The roles of (epi)genetics, the postnatal environment and the fetus are also discussed. We conclude that maternal prenatal psychosocial stress is a complex phenomenon that affects maternal emotions, behavior and physiology in many ways, and may influence the physiology and functioning of the fetus through a network of different pathways. The review concludes with recommendations for future research that helps our understanding of the mechanisms by which maternal prenatal stress exerts its effect on the fetus.

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Interferon-γ and tumor necrosis factor-α sensitize primarily resistant human endometrial stromal cells to Fas-mediated apoptosis

Cited by 52 publications

References 39 publications

NF-κB-dependent cytokine secretion controls Fas expression on chemotherapy-induced premature senescent tumor cells

NF-κB-dependent cytokine secretion controls Fas expression on chemotherapy-induced premature senescent tumor cells

IFN-γ and indoleamine 2,3-dioxygenase signaling between donor dendritic cells and T cells regulates graft versus host and graft versus leukemia activity

Mechanisms underlying the effects of prenatal psychosocial stress on child outcomes: beyond the HPA axis

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