Glucocorticoids and natural killer cells: A suppressive relationship

Muscari, Isabella; Fierabracci, Alessandra; Adorisio, Sabrina; Moretti, Martina; Cannarile, Lorenza; Hong, Vu; Ayroldi, Emira; Delfino, Domenico Vittorio

doi:10.1016/j.bcp.2022.114930

Cited by 15 publications

(6 citation statements)

References 100 publications

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“…Glucocorticoids are considered immunosuppressors, since they inhibit several immune cell activities (Van Laethem et al 2001 ; Strehl et al 2019 ). For example, they are able to suppress T-cell activation and NK-cell activity (Muscari et al 2022 ), which is in line with the effects observed with PFOS and DEP exposure, both substances able to activate glucocorticoid receptor. Regarding T helper cells differentiation, glucocorticoids are able to suppress T helper cells, together with their effector functions (Liberman et al 2018 ; Strehl et al 2019 ; Taves and Ashwell 2021 ).…”

Section: Discussionsupporting

confidence: 53%

Impact of endocrine disruptors on peripheral blood mononuclear cells in vitro: role of gender

Maddalon,

Cari,

Iulini

et al. 2023

Arch Toxicol

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Humans can be exposed to endocrine disruptors (EDs) in numerous ways. EDs can interfere with endogenous hormones at different levels, resulting in numerous adverse human health outcomes, including immunotoxicity. In this regard, this study aimed to investigate in vitro the possible effects of EDs on immune cells and possible gender differences. Peripheral blood mononuclear cells from healthy humans, both males and females, were exposed to 6 different EDs, namely atrazine (herbicide), cypermethrin (insecticide), diethyl phthalate (plasticizer), 17α-ethynylestradiol (contraceptive drug), perfluorooctanesulfonic acid (persistent organic pollutant), and vinclozolin (fungicide). We evaluated the effect of EDs on RACK1 (receptor for activated C kinase 1) expression, considering it as a bridge between the endocrine and the immune system, and putatively used as screening tool of immunotoxic effects of EDs. The exposure to EDs resulted at different extent in alteration in RACK1 expression, pro-inflammatory activity, natural killer lytic ability, and lymphocyte differentiation, with sex-related differences. In particular, diethyl phthalate and perfluorooctanesulfonic acid resulted the most active EDs tested, with gender differences in terms of effects and magnitude. The results from our study evidenced the ability of EDs to directly affect immune cells.

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Section: Discussionsupporting

confidence: 53%

Impact of endocrine disruptors on peripheral blood mononuclear cells in vitro: role of gender

Maddalon,

Cari,

Iulini

et al. 2023

Arch Toxicol

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“…The development of cancer metastases is particularly affected by the inhibition of immune activity associated with immune checkpoints (ICP), especially the PD1 (programmed death receptor 1) present, among others, on CD8+ T cells, natural killer cells and macrophages, and its ligand PD-L1 (programmed death receptor ligand 1) presented on cancer cells ( 31 , 32 ). Our primary results show a reduction in PD-L1 expression in the brain tissue of two different species of animals in two animal models of depression (Curzytek K, Malicki S, Kubera MW, Maes M, et al., paper in preparation).…”

Section: Discussionmentioning

confidence: 99%

Stimulatory effect of fluoxetine and desipramine, but not mirtazapine on C26 colon carcinoma hepatic metastases formation: association with cytokines

et al. 2023

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Due to the high prevalence of depression among cancer patients, antidepressant medications are frequently administered as adjuvant treatment. However, the safety of such medications in the development of metastasis is unclear. In this study, we investigated the effects of fluoxetine, desipramine, and mirtazapine on the liver metastasis of murine C26 colon carcinoma (cc). Balb/c male mice were administered these antidepressants intraperitoneally (i.p.) for 14 days following intrasplenic injections of C26 colon carcinoma cells. Desipramine and fluoxetine, but not mirtazapine, significantly increased the number of tumor foci and total volume of the tumor in liver tissue. This effect was associated with a decrease in the ability of splenocytes to produce interleukin (IL)-1β and interferon (IFN)-γ and an increase in their ability to produce interleukin (IL)-10. Similar changes were observed in plasma IL-1β, IFN-γ, and IL-10 levels. The current study demonstrates that the stimulatory effect of desipramine and fluoxetine, but not mirtazapine, on experimental colon cancer liver metastasis is associated with a suppression of immune defenses against the tumor.

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“…Thus, antiproliferative agents are also inhibitors of B cell proliferation. In addition to their role on T cell activation and proliferation, glucocorticoids are known to affect B cell, neutrophil, macrophage, DC and NK cell activation and/or proliferation ( Allison and Eugui, 2000 ; Muscari et al., 2022 ).…”

Section: Immunosuppressive Drugmentioning

confidence: 99%

Solid organ transplantation and gut microbiota: a review of the potential immunomodulatory properties of short-chain fatty acids in graft maintenance

Jardou,

Brossier,

Marquet

et al. 2024

Front. Cell. Infect. Microbiol.

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Transplantation is the treatment of choice for several end-stage organ defects: it considerably improves patient survival and quality of life. However, post-transplant recipients may experience episodes of rejection that can favor or ultimately lead to graft loss. Graft maintenance requires a complex and life-long immunosuppressive treatment. Different immunosuppressive drugs (i.e., calcineurin inhibitors, glucocorticoids, biological immunosuppressive agents, mammalian target of rapamycin inhibitors, and antiproliferative or antimetabolic agents) are used in combination to mitigate the immune response against the allograft. Unfortunately, the use of these antirejection agents may lead to opportunistic infections, metabolic (e.g., post-transplant diabetes mellitus) or cardiovascular (e.g., arterial hypertension) disorders, cancer (e.g., non-Hodgkin lymphoma) and other adverse effects. Lately, immunosuppressive drugs have also been associated with gut microbiome alterations, known as dysbiosis, and were shown to affect gut microbiota-derived short-chain fatty acids (SCFA) production. SCFA play a key immunomodulatory role in physiological conditions, and their impairment in transplant patients could partly counterbalance the effect of immunosuppressive drugs leading to the activation of deleterious pathways and graft rejection. In this review, we will first present an overview of the mechanisms of graft rejection that are prevented by the immunosuppressive protocol. Next, we will explain the dynamic changes of the gut microbiota during transplantation, focusing on SCFA. Finally, we will describe the known functions of SCFA in regulating immune-inflammatory reactions and discuss the impact of SCFA impairment in immunosuppressive drug treated patients.

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Glucocorticoids and natural killer cells: A suppressive relationship

Cited by 15 publications

References 100 publications

Impact of endocrine disruptors on peripheral blood mononuclear cells in vitro: role of gender

Impact of endocrine disruptors on peripheral blood mononuclear cells in vitro: role of gender

Stimulatory effect of fluoxetine and desipramine, but not mirtazapine on C26 colon carcinoma hepatic metastases formation: association with cytokines

Solid organ transplantation and gut microbiota: a review of the potential immunomodulatory properties of short-chain fatty acids in graft maintenance

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