Tumor Necrosis Factor-related Apoptosis-inducing Ligand (TRAIL) Induces Rheumatoid Arthritis Synovial Fibroblast Proliferation through Mitogen-activated Protein Kinases and Phosphatidylinositol 3-Kinase/Akt

Morel, Jacques; Audo, Rachel; Hahne, Michael; Combe, Bernard

doi:10.1074/jbc.m414469200

Cited by 154 publications

(168 citation statements)

References 33 publications

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“…In addition to apoptosis, the binding of TRAIL to its receptors can also induce a variety of nonapoptotic activities (12)(13)(14)(15)(16) and contributes in a complex manner to T cell activation. For example, in vitro data indicate that TRAIL can either suppress or costimulate T cell responses depending on whether it acts as a ligand or as a receptor, respectively (17)(18)(19).…”

Section: T Cell Trail Promotes Murine Lupus By Sustaining Effectormentioning

confidence: 99%

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T Cell TRAIL Promotes Murine Lupus by Sustaining Effector CD4 Th Cell Numbers and by Inhibiting CD8 CTL Activity

Rus

Nguyen

Puliaev

et al. 2007

The Journal of Immunology

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T cells play an essential role in driving humoral autoimmunity in lupus. Molecules such as TRAIL exhibit strong T cell modulatory effects and are up-regulated in lupus, raising the possibility that they may influence disease severity. To address this possibility, we examined the role of TRAIL expression on pathogenic T cells in an induced model of murine lupus, the parent-into-F1 (P→F1) model of chronic graft-vs-host disease (GVHD), using wild-type or TRAIL-deficient donor T cells. Results were compared with mice undergoing suppressive acute GVHD. Although chronic GVHD mice exhibited less donor T cell TRAIL up-regulation and IFN-α-inducible gene expression than acute GVHD mice, donor CD4+ T cell TRAIL expression in chronic GVHD was essential for sustaining effector CD4+ Th cell numbers, for sustaining help to B cells, and for more severe lupus-like renal disease development. Conversely, TRAIL expression on donor CD8+ T cells had a milder, but significant down-regulatory effect on CTL effector function, affecting the perforin/granzyme pathway and not the Fas ligand pathway. These results indicate that, in this model, T cell-expressed TRAIL exacerbates lupus by the following: 1) positively regulating CD4+ Th cell numbers, thereby sustaining T cell help for B cells, and 2) to a lesser degree by negatively regulating perforin-mediated CD8+ CTL killing that could potentially eliminate activated autoreactive B cells.

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Section: T Cell Trail Promotes Murine Lupus By Sustaining Effectormentioning

confidence: 99%

“…Given the dual role of TRAIL in both proliferation and apoptosis (11,13,14), the increased engraftment of TRAIL KO donor CD8 ϩ T cells at day 10 ( Fig. 2C) could be the consequence of increased proliferation and/or decreased apoptosis.…”

Section: Increased Engraftment Of Trail Ko Donor Cd8 ϩ Cells In Acutementioning

confidence: 99%

T Cell TRAIL Promotes Murine Lupus by Sustaining Effector CD4 Th Cell Numbers and by Inhibiting CD8 CTL Activity

Rus

Nguyen

Puliaev

et al. 2007

The Journal of Immunology

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“…In normal cells that are generally resistant to the apoptotic effects, TRAIL induces proliferation of vascular smooth muscle cells, synovial fibroblasts and T lymphocytes [9][10][11]. Similarly, TRAIL treatment stimulated proliferation of apoptosis-resistant malignant cells, such as leukemia, neuroblastoma, renal cell carcinoma, and colon carcinoma cell lines [8,12,13].…”

Section: Introductionmentioning

confidence: 99%

Multiple effects of TRAIL in human carcinoma cells: Induction of apoptosis, senescence, proliferation, and cytokine production

Levina

Marrangoni

DeMarco

et al. 2008

Experimental Cell Research

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TRAIL is a death ligand that induces apoptosis in malignant but not normal cells. Recently the ability of TRAIL to induce proliferation in apoptosis-resistant normal and malignant cells was reported. In this study, we analyzed TRAIL effects in apoptosis sensitive MCF7, OVCAR3 and H460 human tumor cell lines. TRAIL at low concentrations preferentially induced cell proliferation. At 100 ng/ ml apoptotic death was readily observed, however surviving cells acquired higher proliferative capacity. TRAIL stimulated production of several cytokines, IL-8, RANTES, MCP-1 and bFGF, and activation of caspases 1 and 8 was essential for this effect. Antibodies to IL-8, RANTES, and bFGF blocked TRAIL-induced cell proliferation and further stimulated apoptosis. For the first time, we report that high TRAIL concentrations induced cell senescence as determined by altered morphology and expression of several senescence markers: SA-β-gal, p21 Waf1/Cip1 , p16 INK4a , and HMGA. Caspase 9 inhibition protected TRAIL-treated cells from senescence, whereas inhibition of caspases 1 and 8 increased yield of SLP cells. In conclusion, in cultured human carcinoma cells, TRAIL therapy results in three functional outcomes, apoptosis, proliferation and senescence. TRAIL induced proapoptotic and prosurvival responses correlate with strength of signaling. TRAIL-induced cytokine production is responsible for its proliferative and prosurvival effects.

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“…In other case, mice in which Bcl-xl-overexpressing Colo357 pancreatic ductal carcinomas were orthotopic transplanted formed more metastases upon TRAIL treatment (Trauzold et al, 2006), and finally two studies with blasts from leukemia patients treated ex vivo report effects of TRAIL exposure ranging from triggering of cell death to induction of cell proliferation (Ehrhardt et al, 2003;Hasegawa et al, 2005). TRAIL-induced proliferative effect has also been reported in synoviocytes from human rheumatoid patients who exhibit a poorly understood biphasic response to the cytokine, as it triggers death in an initial phase but support proliferation for the persisting/resistant cell fraction (Morel et al, 2005). These results suggest that in the case of TRAIL resistance in cancer cells or specific inflammatory conditions, cells may switch the TRAIL response from apoptotic to proliferative.…”

Section: Novel Paradigms For Cancer Therapy V Pavet Et Almentioning

confidence: 99%

Towards novel paradigms for cancer therapy

et al. 2010

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Cancer is a complex progressive multistep disorder that results from the accumulation of genetic and epigenetic abnormalities, which lead to the transformation of normal cells into malignant derivatives. Despite enormous progress in the understanding of cancer biology including the decryption of multiple regulatory networks governing cell growth and death, and despite the possibility of analyzing (epi)genetic deregulation at the genome-wide scale, cancertargeted therapy is still the exception. In fact, to date there are still far too few examples of therapies leading to cure; treatment-derived toxicity is a major issue, and cancer remains to be one of the largest causes of death worldwide. The purpose of this review is to discuss the state of the art of cancer therapy with respect to the key issue of any treatment, namely its target selectivity. Therefore, we recapitulate and discuss current concepts and therapies targeting tumorspecific features, including oncofusion proteins, aberrant kinase activities and epigenetic tumor makeup. We analyze strategies designed to induce tumor-selective death such as the use of oncolytic virus, tumoricidal proteins (NS1, Eorf4, apoptin, HAMLET (human a-lactalbumin made lethal to tumor cells)) and activation of signaling pathways involved in tumor surveillance. We emphasize the potential of the tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) pathway, an essential component of the evolutionary developed defense systems that eradicate malignant cells. Finally, we discuss the necessity of targeting tumor-initiating cells (TICs) to avoid relapse and increase the chances of complete remission, and describe emerging concepts that might provide novel avenues for cancer therapy.

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Tumor Necrosis Factor-related Apoptosis-inducing Ligand (TRAIL) Induces Rheumatoid Arthritis Synovial Fibroblast Proliferation through Mitogen-activated Protein Kinases and Phosphatidylinositol 3-Kinase/Akt

Cited by 154 publications

References 33 publications

T Cell TRAIL Promotes Murine Lupus by Sustaining Effector CD4 Th Cell Numbers and by Inhibiting CD8 CTL Activity

T Cell TRAIL Promotes Murine Lupus by Sustaining Effector CD4 Th Cell Numbers and by Inhibiting CD8 CTL Activity

Multiple effects of TRAIL in human carcinoma cells: Induction of apoptosis, senescence, proliferation, and cytokine production

Towards novel paradigms for cancer therapy

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