Identification and characterization of glucocorticoid-regulated nuclease(s) in lymphoid cells undergoing apoptosis

Caron-Leslie, Lu-Ann M.; Schwartzman, Robert A.; Gaido, Marcia L.; Compton, Mark M.; Cidlowski, John A.

doi:10.1016/0960-0760(91)90288-g

Cited by 51 publications

(14 citation statements)

References 34 publications

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“…The anti-inflammatory and immune-modulatory effects of glucocorticoids and GC-induced apoptosis have led to the use of steroid therapy as an invaluable part of treatment in many clinical settings. High doses of glucocorticoids are well-known to induce apoptosis in thymocytes [66,67], T cells [68], B cells [69], macrophages [70], mature but not immature dendritic cells [71], eosinophils [72], and natural killer cells [73]. Interestingly, glucocorticoids have the opposite effect in neutrophils and actually protect these cells from apoptosis [72,74].…”

Section: Gc-induced Apoptosis In Organ Systemsmentioning

confidence: 99%

Tissue-Specific Actions of Glucocorticoids on Apoptosis: A Double-Edged Sword

Gruver-Yates

Cidlowski

2013

Cells

129

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First described for their metabolic and immunosuppressive effects, glucocorticoids are widely prescribed in clinical settings of inflammation. However, glucocorticoids are also potent inducers of apoptosis in many cell types and tissues. This review will focus on the established mechanisms of glucocorticoid-induced apoptosis and outline what is known about the apoptotic response in cells and tissues of the body after exposure to glucocorticoids. Glucocorticoid-induced apoptosis affects the skeletal system, muscular system, circulatory system, nervous system, endocrine system, reproductive system, and the immune system. Interestingly, several cell types have an anti-apoptotic response to glucocorticoids that is cytoprotective. Lastly, we will discuss the pro- and anti-apoptotic effects of glucocorticoids in cancers and their clinical implications.

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Section: Gc-induced Apoptosis In Organ Systemsmentioning

confidence: 99%

Tissue-Specific Actions of Glucocorticoids on Apoptosis: A Double-Edged Sword

Gruver-Yates

Cidlowski

2013

Cells

129

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“…While such infections are generally controlled by locally residing CD8 + T cells (Liu et al, 2000; Reading et al, 2006), the virus can spread to the brain in neonates as well as immunosuppressed adults, and result in herpes simplex encephalitis (HSE). As glucocorticoids are known to induce apoptosis of T lymphocytes (Blewitt et al, 1983; Caron-Leslie et al, 1991; Cohen and Duke, 1984; Wyllie, 1980), heightened levels of these hormones during HSV infection are associated with immunosuppression, viral spread to the CNS, reactivation of latent virus, and HSE (Freeman et al, 2007; Kusnecov et al, 1992; Nair et al, 2007). Therefore, HSE-associated pathogenesis could be better controlled, if not averted, by a clearer understanding of the immune response following this route of infection, as well as steps at which glucocorticoid-mediated failures in such a response occur.…”

Section: Introductionmentioning

confidence: 99%

Psychological stress impairs the local CD8+ T cell response to mucosal HSV-1 infection and allows for increased pathogenicity via a glucocorticoid receptor-mediated mechanism

Ashcraft

Hunzeker

Bonneau

2008

Psychoneuroendocrinology

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Summary Psychological stress and its associated increases in corticosterone are generally immunosuppressive and contribute to increased herpes simplex virus (HSV)-associated pathogenicity. However, the impact of stress on local control of the initial mucosal-based HSV infection has not been elucidated, nor have the ramifications of such failures of the immune response in terms of viral spread. To address these gaps in knowledge, the studies described herein sought to determine how psychological stress and associated increases in corticosterone may increase susceptibility to HSV encephalitis by allowing for increased viral titers at the site of initial infection. We have shown that in mice intranasally infected with HSV-1, a cell-mediated immune response occurs in the nasopharyngeal-associated lymphoid tissue (NALT), mediastinal lymph nodes (MLN), and superficial cervical lymph nodes (CLN). However, psychological stress induced by restraint decreased the number of lymphocytes in these tissues in HSV-infected mice. Surprisingly, the effects of this restraint stress on HSV-specific CTL function varied by immune tissue. Increased viral titers were found in the nasal cavity of stressed mice, an observation which correlated with an increased CD8+ cell response in the CLN. These findings led us to extend our studies to also determine the ramifications of decreased numbers of locally-derived lymphocytes on viral titers following infection. Using an approach in which the NALT was surgically removed prior to infection, we confirmed that decreased numbers of NALT-derived lymphocytes at the time of infection allows for increased viral replication. We conclude that the increased viral titers observed in mice experiencing psychological stress are the consequence of a glucocorticoid-mediated reduction in the numbers of lymphocytes responsible for resolving the initial infection.

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“…Future studies will pinpoint which one or more of these events are hindered in our stress model. In addition, it has long been recognized that stress and associated increases in corticosterone lead to increased lymphocyte apoptosis (Blewitt et al, 1983;Caron-Leslie et al, 1991;Cohen and Duke, 1984;Wyllie, 1980), an event which may also contribute to the reduced numbers of CD8 + T cells.…”

Section: Restraint Stress Decreases Iln-derived Hsv-specific T Cell Nmentioning

confidence: 99%

Psychological stress exacerbates primary vaginal herpes simplex virus type 1 (HSV-1) infection by impairing both innate and adaptive immune responses

Ashcraft¹,

Bonneau²

2008

Brain, Behavior, and Immunity

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Chronic psychological stress is generally immunosuppressive and contributes to an increase in herpes simplex virus (HSV) pathogenicity. We have previously shown that mice experiencing stress at the time of intranasal HSV infection have increased levels of infectious virus in their nasal cavity, as compared to control mice that were not subjected to stress. We have extended our studies to determine the effects of stress at another clinically-relevant mucosal site by examining the immune response to and pathogenesis of vaginal HSV infection. Mice experiencing psychological stress during vaginal HSV infection exhibited an increase in both vaginal viral titers and the pathology associated with this HSV infection. We demonstrate that these observations result from the failure of both the innate and HSV-specific adaptive immune responses. At two days post-infection, NK cell numbers were significantly decreased in mice experiencing restraint stress. Studies examining the adaptive immune response revealed a decrease in the number of HSV-specific CD8 + T cells in not only the vaginal tissue itself but also the draining iliac lymph nodes (ILN). Furthermore, the number of functional cells, in terms of both their degranulation and interferon-γ production, in the ILN of stressed mice was decreased as compared to non-stressed mice. We conclude that psychological stress, through its suppression of both innate and adaptive immune responses, may be an important factor in the ability to control vaginal HSV infection.

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Identification and characterization of glucocorticoid-regulated nuclease(s) in lymphoid cells undergoing apoptosis

Cited by 51 publications

References 34 publications

Tissue-Specific Actions of Glucocorticoids on Apoptosis: A Double-Edged Sword

Tissue-Specific Actions of Glucocorticoids on Apoptosis: A Double-Edged Sword

Psychological stress impairs the local CD8+ T cell response to mucosal HSV-1 infection and allows for increased pathogenicity via a glucocorticoid receptor-mediated mechanism

Psychological stress exacerbates primary vaginal herpes simplex virus type 1 (HSV-1) infection by impairing both innate and adaptive immune responses

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