The Experts below are selected from a list of 303 Experts worldwide ranked by ideXlab platform
John F. Sheridan - One of the best experts on this subject based on the ideXlab platform.
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64. Roles of glucocorticoid receptor and microRNA in repeated Social Disruption stress-induced glucocorticoid resistance in splenic macrophages
Brain Behavior and Immunity, 2014Co-Authors: S.h. Jung, Yue Wang, A.j. Tarr, Brenda F. Reader, John F. SheridanAbstract:Chronic Social stress has attracted interest due to its deleterious impact on health psychologically and physiologically. It has been shown using rodent models of chronic Social stress, e.g., repeated Social Disruption stress (RSD), innate immune cells develop insensitivity to glucocorticoid (GC) stimuli and contribute to enhance inflammatory responses. Previous studies have found that one of the immune cells that is GC insensitive in response to RSD is the splenic macrophage, however, the underlying molecular mechanisms that contribute to this process are not fully understood. Current data showed RSD modified GC receptor expression and increased the expression ratio of FK506-binding protein 51 (FKBP51) to FKBP52, favoring to blockade of nuclear translocation of GC–GC receptor complexes in splenic macrophages. Using a NanoString nCounter miRNA Expression assay and the internet-based DIANA-micro T-CDS database (ver 5.0), the expression of 6 microRNAs was increased by RSD. The two highest expressed miRNAs (miRNA-29b and 340) were overexpressed in L929 cells and were found to completely block LPS-induced overexpression of GC receptors. These data suggest that miRNAs play a critical role in RSD-induced GC resistance in splenic macrophages, especially via an epigenetic mechanism of GC receptor expression at least. This was supported by grants funded through NIH/NIMH: R01MH093473 and R01MH097243.
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Beta adrenergic blockade decreases the immunomodulatory effects of Social Disruption stress.
Brain behavior and immunity, 2012Co-Authors: Mark L. Hanke, Michael T. Bailey, Nicole D. Powell, Latonia Stiner, John F. SheridanAbstract:During physiological or psychological stress, catecholamines produced by the sympathetic nervous system (SNS) regulate the immune system. Previous studies report that the activation of β-adrenergic receptors (βARs) mediates the actions of catecholamines and increases pro-inflammatory cytokine production in a number of different cell types. The impact of the SNS on the immune modulation of Social defeat has not been examined. The following studies were designed to determine whether SNS activation during Social Disruption stress (SDR) influences anxiety-like behavior as well as the activation, priming, and glucocorticoid resistance of splenocytes after Social stress. CD-1 mice were exposed to one, three, or six cycles of SDR and HPLC analysis of the plasma and spleen revealed an increase in catecholamines. After six cycles of SDR the open field test was used to measure behaviors characteristic of anxiety and indicated that the Social defeat induced increase in anxiety-like behavior was blocked by pre-treatment with the β-adrenergic antagonist propranolol. Pre-treatment with the β-adrenergic antagonist propranolol did not significantly alter corticosterone levels indicating no difference in activation of the hypothalamic–pituitary–adrenal axis. In addition to anxiety-like behavior the SDR induced splenomegaly and increase in plasma IL-6, TNFα, and MCP-1 were each reversed by pre-treatment with propranolol. Furthermore, flow cytometric analysis of cells from propranolol pretreated mice reduced the SDR-induced increase in the percentage of CD11b+ splenic macrophages and significantly decreased the expression of TLR2, TLR4, and CD86 on the surface of these cells. In addition, supernatants from 18 h LPS-stimulated ex vivo cultures of splenocytes from propranolol-treated SDR mice contained less IL-6. Likewise propranolol pre-treatment abrogated the glucocorticoid insensitivity of CD11b+ cells ex vivo when compared to splenocytes from SDR vehicle-treated mice. Together, this study demonstrates that the immune activation and priming effects of SDR result, in part, as a consequence of SNS activation.
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β-Adrenergic receptor mediated increases in activation and function of natural killer cells following repeated Social Disruption
Brain behavior and immunity, 2012Co-Authors: A.j. Tarr, Nicole D. Powell, Brenda F. Reader, Neela Bhave, John F. SheridanAbstract:Natural killer (NK) cells are specialized innate lymphocytes important in the early defense against tumor and virus bearing cells. Many factors influence the immune system's effectiveness against pathogens, including stress. Social Disruption (SDR) "primes" macrophages/monocytes and dendritic cells thereby enhancing their anti-microbial function. What remains unclear is whether similar responses are evident in NK cells. Current studies investigated the cellular distribution and activation/inhibitory phenotypes of NK cells in the spleen, lung, and blood of C57BL/6 male mice following SDR. Furthermore, cytolytic activity and anti-viral cytokine production of splenic NK cells were determined. Lastly, β-adrenergic receptor (β-AR) signaling was investigated to determine possible mechanisms behind the SDR-induced NK cell alterations. Results indicated NK cells from SDR mice have increased expression of CD16 and CD69 and reduced NKG2a and Ly49a expression on splenic CD3-/DX5+ NK cells indicative of an activated phenotype, both immediately and 14h post-SDR. Administration of propranolol (10mg/kg; non-selective β-adrenergic receptor antagonist) was shown to block these "priming" effects at the 14h time-point. In the lung, SDR had similar effects on activation and inhibitory receptors 14h post-SDR, however no alterations were evident in the blood besides increased NK cells directly after SDR. Additionally, splenic NK cells from SDR mice had increased CD107a surface expression, cytolytic activity, and IFN-γ production was increased upon costimulation with IgG and IL-2 ex vivo. Collectively, these data suggest that Social stress "primes" NK cells in the spleen and lung to be more proficient in their cytolytic and anti-viral/tumor effecter functions through β-adrenergic receptor dependent signaling.
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Social Disruption induces lung inflammation.
Brain behavior and immunity, 2009Co-Authors: Jennifer M. Curry, Mark L. Hanke, Melissa G. Piper, Michael T. Bailey, Benjamin D. Bringardner, John F. Sheridan, Clay B. MarshAbstract:Social Disruption (SDR) is a well-characterized mouse stressor that causes changes in immune cell reactivity in response to inflammatory stimuli. In this study, we found that SDR in the absence of an immune challenge induced pulmonary inflammation and increased pulmonary myeloperoxidase activity. The percentage of neutrophils within the lungs increased 2-fold after Social Disruption. Monocyte accumulation in the lungs was also significantly increased. In addition, SDR increased the percentage of neutrophils that expressed CD11b, indicating that more neutrophils were in an activated state. In the lungs, we observed an increased level of the inflammatory cytokine, IL-1β, as well as higher levels of KC/CXCL1, MIP-2/CXCL2, and MCP-1/CCL2, which are chemokines responsible for neutrophil and monocyte recruitment. Furthermore, Social Disruption led to increased lung expression of the adhesion molecules P-selectin, E-selectin, and ICAM-1, which localize and recruit immune cells. These data support previous findings of an inflammatory environment induced by SDR. We demonstrate that this effect also occurs in the pulmonary milieu and in the absence of an inflammatory stimulus.
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repeated Social defeat causes increased anxiety like behavior and alters splenocyte function in c57bl 6 and cd 1 mice
Brain Behavior and Immunity, 2007Co-Authors: Steven G Kinsey, Michael T. Bailey, John F. Sheridan, David A Padgett, Ronit AvitsurAbstract:The experimental model, Social Disruption (SDR), is a model of Social stress in which mice are repeatedly attacked and defeated in their home cage by an aggressive conspecific. In terms of the impact of this stressor on the immune response, SDR has been reported to cause hyperinflammation and glucocorticoid insensitivity. To this point however, the behavioral consequences of SDR have not been thoroughly characterized. Because Social defeat has been reported to cause anxiety- and depressive-like behaviors, the current study was designed to assess whether SDR also causes anxiety- and depressive-like behaviors. Using the light/dark preference test and the open field test as tools to measure behaviors characteristic of anxiety, the data showed that C57BL/6 and CD-1 male mice subjected to SDR displayed increased anxiety-like behavior. The increase in anxiety-like behaviors persisted for at least 1 week after the cessation of the stressor. In contrast, depressive-like behaviors were not elicited by SDR as assessed by the forced swim test or the tail suspension test. These data indicate that Social Disruption stress causes an increase in anxiety-like behaviors, but not depressive-like behaviors.
Ronit Avitsur - One of the best experts on this subject based on the ideXlab platform.
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repeated Social defeat causes increased anxiety like behavior and alters splenocyte function in c57bl 6 and cd 1 mice
Brain Behavior and Immunity, 2007Co-Authors: Steven G Kinsey, Michael T. Bailey, John F. Sheridan, David A Padgett, Ronit AvitsurAbstract:The experimental model, Social Disruption (SDR), is a model of Social stress in which mice are repeatedly attacked and defeated in their home cage by an aggressive conspecific. In terms of the impact of this stressor on the immune response, SDR has been reported to cause hyperinflammation and glucocorticoid insensitivity. To this point however, the behavioral consequences of SDR have not been thoroughly characterized. Because Social defeat has been reported to cause anxiety- and depressive-like behaviors, the current study was designed to assess whether SDR also causes anxiety- and depressive-like behaviors. Using the light/dark preference test and the open field test as tools to measure behaviors characteristic of anxiety, the data showed that C57BL/6 and CD-1 male mice subjected to SDR displayed increased anxiety-like behavior. The increase in anxiety-like behaviors persisted for at least 1 week after the cessation of the stressor. In contrast, depressive-like behaviors were not elicited by SDR as assessed by the forced swim test or the tail suspension test. These data indicate that Social Disruption stress causes an increase in anxiety-like behaviors, but not depressive-like behaviors.
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Social Disruption, Immunity, and Susceptibility to Viral Infection: Role of Glucocorticoid Insensitivity and NGF
Annals of the New York Academy of Sciences, 2006Co-Authors: John F. Sheridan, Ronit Avitsur, Jennifer L Stark, David A PadgettAbstract:Glucocorticoid (cort) responses have been shown to suppress inflammatory reactions by inhibiting the trafficking of immune cells. Recently, it was demonstrated that restraint stress (RST) and psychoSocial stress (Social reorganization; SRO) differentially affected the pathophysiology and survival in the mouse influenza viral infection model. While both stressors activated the HPA axis, only SRO affected survival. In RST, elevated cort diminished recruitment of inflammatory cells following intranasal challenge of C57BL/6 mice with A/PR8 virus. However, infected SRO mice developed hypercellularity in the lungs and were more likely to die from lung consolidation than controls. Since elevated cort failed to be anti-inflammatory in SRO mice, the hypothesis that psychoSocial stress induced steroid insensitivity was tested. An in vitro cort suppression test was performed by stimulating splenocytes from SRO and control mice with mitogen in the presence or absence of cort. Proliferation of ConA-stimulated cells was inhibited by cort in a dose-dependent fashion in controls, but splenocytes from SRO mice stimulated with ConA were resistant to cort-induced suppression. Thus, psychoSocial stress induced a state of steroid insensitivity. SRO also induced the release of nerve growth factor (NGF) from the salivary glands into circulation; plasma NGF correlated with development of steroid insensitivity. NGF has been reported to negatively regulate the expression of type II glucocorticoid receptors, and thus may be a key factor in the induction of steroid insensitivity.
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Social Disruption-induced glucocorticoid resistance: kinetics and site specificity.
Journal of neuroimmunology, 2002Co-Authors: Ronit Avitsur, Jennifer L Stark, Firdaus S Dhabhar, David A Padgett, John F. SheridanAbstract:Social Disruption (SDR) of male mice has been shown to induce a state of functional glucocorticoid (GC) resistance in splenocytes. The present study demonstrated that GC resistance developed following repeated, but not acute exposure to SDR. GC resistance was long-lasting and persisted for at least 10 days after stress. In contrast, SDR did not alter cytokine secretion from peritoneal mononuclear cells treated with corticosterone. These findings suggest that SDR-induced GC resistance may be restricted to specific sites such as the spleen.
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Interleukin-6 and the development of Social Disruption-induced glucocorticoid resistance.
Journal of neuroimmunology, 2002Co-Authors: Jennifer L Stark, Ronit Avitsur, David A Padgett, John Hunzeker, John F. SheridanAbstract:Following Social Disruption (SDR) stress in male mice, corticosterone resistance of splenocytes was accompanied by enhanced LPS-stimulated interleukin (IL)-6 secretion. The present study examined the role of IL-6 in the development of corticosterone resistance. Addition of IL-6 to control splenocyte cultures did not induce corticosterone resistance. SDR also elevated IL-6 in plasma and liver, but not in spleen. IL-6 deficient mice that were exposed to SDR developed glucocorticoid resistance despite the absence of systemic IL-6. These findings suggest that although SDR enhanced IL-6 responses, IL-6 was not essential for the development of stress-induced splenocyte corticosterone resistance.
David A Padgett - One of the best experts on this subject based on the ideXlab platform.
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repeated Social defeat causes increased anxiety like behavior and alters splenocyte function in c57bl 6 and cd 1 mice
Brain Behavior and Immunity, 2007Co-Authors: Steven G Kinsey, Michael T. Bailey, John F. Sheridan, David A Padgett, Ronit AvitsurAbstract:The experimental model, Social Disruption (SDR), is a model of Social stress in which mice are repeatedly attacked and defeated in their home cage by an aggressive conspecific. In terms of the impact of this stressor on the immune response, SDR has been reported to cause hyperinflammation and glucocorticoid insensitivity. To this point however, the behavioral consequences of SDR have not been thoroughly characterized. Because Social defeat has been reported to cause anxiety- and depressive-like behaviors, the current study was designed to assess whether SDR also causes anxiety- and depressive-like behaviors. Using the light/dark preference test and the open field test as tools to measure behaviors characteristic of anxiety, the data showed that C57BL/6 and CD-1 male mice subjected to SDR displayed increased anxiety-like behavior. The increase in anxiety-like behaviors persisted for at least 1 week after the cessation of the stressor. In contrast, depressive-like behaviors were not elicited by SDR as assessed by the forced swim test or the tail suspension test. These data indicate that Social Disruption stress causes an increase in anxiety-like behaviors, but not depressive-like behaviors.
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Social Disruption, Immunity, and Susceptibility to Viral Infection: Role of Glucocorticoid Insensitivity and NGF
Annals of the New York Academy of Sciences, 2006Co-Authors: John F. Sheridan, Ronit Avitsur, Jennifer L Stark, David A PadgettAbstract:Glucocorticoid (cort) responses have been shown to suppress inflammatory reactions by inhibiting the trafficking of immune cells. Recently, it was demonstrated that restraint stress (RST) and psychoSocial stress (Social reorganization; SRO) differentially affected the pathophysiology and survival in the mouse influenza viral infection model. While both stressors activated the HPA axis, only SRO affected survival. In RST, elevated cort diminished recruitment of inflammatory cells following intranasal challenge of C57BL/6 mice with A/PR8 virus. However, infected SRO mice developed hypercellularity in the lungs and were more likely to die from lung consolidation than controls. Since elevated cort failed to be anti-inflammatory in SRO mice, the hypothesis that psychoSocial stress induced steroid insensitivity was tested. An in vitro cort suppression test was performed by stimulating splenocytes from SRO and control mice with mitogen in the presence or absence of cort. Proliferation of ConA-stimulated cells was inhibited by cort in a dose-dependent fashion in controls, but splenocytes from SRO mice stimulated with ConA were resistant to cort-induced suppression. Thus, psychoSocial stress induced a state of steroid insensitivity. SRO also induced the release of nerve growth factor (NGF) from the salivary glands into circulation; plasma NGF correlated with development of steroid insensitivity. NGF has been reported to negatively regulate the expression of type II glucocorticoid receptors, and thus may be a key factor in the induction of steroid insensitivity.
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Social Disruption-induced glucocorticoid resistance: kinetics and site specificity.
Journal of neuroimmunology, 2002Co-Authors: Ronit Avitsur, Jennifer L Stark, Firdaus S Dhabhar, David A Padgett, John F. SheridanAbstract:Social Disruption (SDR) of male mice has been shown to induce a state of functional glucocorticoid (GC) resistance in splenocytes. The present study demonstrated that GC resistance developed following repeated, but not acute exposure to SDR. GC resistance was long-lasting and persisted for at least 10 days after stress. In contrast, SDR did not alter cytokine secretion from peritoneal mononuclear cells treated with corticosterone. These findings suggest that SDR-induced GC resistance may be restricted to specific sites such as the spleen.
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Interleukin-6 and the development of Social Disruption-induced glucocorticoid resistance.
Journal of neuroimmunology, 2002Co-Authors: Jennifer L Stark, Ronit Avitsur, David A Padgett, John Hunzeker, John F. SheridanAbstract:Following Social Disruption (SDR) stress in male mice, corticosterone resistance of splenocytes was accompanied by enhanced LPS-stimulated interleukin (IL)-6 secretion. The present study examined the role of IL-6 in the development of corticosterone resistance. Addition of IL-6 to control splenocyte cultures did not induce corticosterone resistance. SDR also elevated IL-6 in plasma and liver, but not in spleen. IL-6 deficient mice that were exposed to SDR developed glucocorticoid resistance despite the absence of systemic IL-6. These findings suggest that although SDR enhanced IL-6 responses, IL-6 was not essential for the development of stress-induced splenocyte corticosterone resistance.
Chris Beyrer - One of the best experts on this subject based on the ideXlab platform.
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burma and cambodia human rights Social Disruption and the spread of hiv aids
Health and Human Rights, 1998Co-Authors: Chris BeyrerAbstract:This article discusses issues on human rights Social Disruption and the spread of HIV/AIDS in Burma and Cambodia. Several studies show that HIV spreads fastest where Social life is chaotic poverty endemic and rights violated which is particularly true in the poorest and most strife-torn nations of the world. However the argument around the issues raised by HIV/AIDS and human rights has focused on the protection of individuals or groups affected by the disease from rights violations. Thus HIV/AIDS prevention and control programs may need to address the prevailing human rights situation in countries suffering from national ethnic or political conflicts. Burma had an epidemic of HIV among its large population of injecting drug users while Cambodia underwent a similar rise in HIV rates among sex workers and their clients. In 1996 Burma had approximately 500000 cases of HIV infection while Cambodia had 50000-90000. To better understand the ongoing spread of HIV in these countries political Social and human rights analyses are necessary.
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Burma and Cambodia: Human Rights, Social Disruption, and the Spread of HIV/AIDS.
Health and human rights, 1998Co-Authors: Chris BeyrerAbstract:The debate around the issues raised by HIV/AIDS and human rights has largely focused on the protection from rights violations of individuals or groups affected by the disease. The relationship between political and Social conditions where human rights abuses are frequent and the spread of HIV infection has been less studied. Two countries in Southeast Asia, Burma and Cambodia, are currently undergoing serious and uncontrolled epidemics of HIV; both are marked by political cultures of state violence and corruption, chronic civil war and insurgency, and widespread human rights violations. This article attempts to investigate associations between rapid HIV spread and political and Social crises, using Burma and Cambodia as case studies. The climate and context of rights abuses are seen as significant factors of national vulnerability to the epidemic spread of HIV/AIDS.
Rick Ruddell - One of the best experts on this subject based on the ideXlab platform.
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Social Disruption, state priorities, and minority threat A cross-national study of imprisonment
Punishment & Society, 2005Co-Authors: Rick RuddellAbstract:Understanding the use of punishment becomes increasingly important as imprisonment rates in many nations have fluctuated irrespective of crime rates. Controlling for violent crime, inequality, modernization, and economic stress, this research examined three diverse hypotheses about the sources of imprisonment in a sample of 100 nations. Consistent with expectations, nations that retained use of the death penalty had a greater use of imprisonment. More surprising was the finding of a clear and consistent relationship between imprisonment and countries with common law legal systems, as well as newly independent nation-states. Finally, this study reveals a significant – although inconsistent – association between population heterogeneity and imprisonment. While punishment research has often focused upon the relationships between economic variables and imprisonment, these findings suggest that theories of formal Social control will remain incomplete until the roles of political, cultural, and structural conditions are fully understood.
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Social Disruption state priorities and minority threat a cross national study of imprisonment
Punishment & Society, 2005Co-Authors: Rick RuddellAbstract:Understanding the use of punishment becomes increasingly important as imprisonment rates in many nations have fluctuated irrespective of crime rates. Controlling for violent crime, inequality, modernization, and economic stress, this research examined three diverse hypotheses about the sources of imprisonment in a sample of 100 nations. Consistent with expectations, nations that retained use of the death penalty had a greater use of imprisonment. More surprising was the finding of a clear and consistent relationship between imprisonment and countries with common law legal systems, as well as newly independent nation-states. Finally, this study reveals a significant – although inconsistent – association between population heterogeneity and imprisonment. While punishment research has often focused upon the relationships between economic variables and imprisonment, these findings suggest that theories of formal Social control will remain incomplete until the roles of political, cultural, and structural condi...
