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Toll-like receptor expression and bactericidal activity are increased in splenic macrophages from socially stressed mice
Abstracts / Brain, Behavior, and Immunity 20 (2006) e1–e16
the effect of acute (60 min) restraint administered immediately before spared nerve injury (SNI) on neuropathic pain. Allodynia was assessed before and 24 h after a single period of restraint and was found to be similar between WT and KO mice. However, 1, 3, 5, and 7 days after SNI, allodynia (assessed by von Frey monofilaments) in the hindpaw ipsilateral to the injury was significantly enhanced in stressed KO mice as compared to stressed WT and non-stressed mice. In addition, mechanical allodynia in the hindpaw contralateral to the injury was enhanced in stressed KO mice compared to stressed WT mice. Cold allodynia (assessed by acetone application) was signficantly increased for stressed KO mice on days 3, 5, and 7 post-SNI in the hindpaw ipsilateral to the injury and overall post-SNI in the hindpaw contralateral to the injury compared to non-stressed KO mice. In summary, male CX3CR1-/- mice exhibit enhanced ipsilateral mechanical allodynia with enhanced mirror image pain following SNI compared to wild-type mice. These effects were potentiated by stress. These data suggest that the absence of the CX3CR1 does not confer protection from the onset of allodynia after peripheral nerve injury. However, other factors (e.g., corticosterone) produced as a result of stress or concomitant injury may enhance neuropathic pain. doi:10.1016/j.bbi.2006.04.005
Toll-like receptor expression and bactericidal activity are increased in splenic macrophages from socially stressed mice Michael T. Bailey a, Harald Engler a, David A. Padgett b, John F. Sheridan b a
Section of Oral Biology, College of Dentistry, The Institute for Behavioral Medicine Research, The Ohio State University, Columbus, OH, USA b Department of Molecular Virology, Immunology and Medical Genetics, The Institute for Behavioral Medicine Research, The Ohio State University, Columbus, OH, USA Background: Phagocytes of the innate immune system represent a first line of defense against invading microbes. Thus, altering the function of these cells can have a profound impact on the course of an infectious challenge. In mice, repeated social defeat significantly alters macrophage functioning by enhancing cytokine production upon stimulation with lipopolysaccharide, suggesting that the macrophages are primed by exposure to the stressor. Because priming is likely to be associated with enhanced toll-like receptor (TLR) expression and bactericidal activity, it was hypothesized that repeated social defeat would increase the expression of TLRs and the ability of splenic macrophages to kill Escherichia coli. Methods: Mice were exposed to social disruption (SDR) stress, by placing an intruder mouse into the cage of five resident mice for 2 h on six consecutive days. On the day following the last cycle, single cell suspensions were created
e3
from the spleen. To determine the impact of SDR on TLR2 and TLR4 expression, magnetic beads ligated to anti-CD11b+ antibodies were used to enrich cultures for CD11b+ cells. Flow cytometry was then used to quantify TLR2 and TLR4 surface expression. In a follow up experiment, bactericidal activity was assessed in cultures standardized by flow cytometry to contain 5 · 104 CD11b+ macrophages. Live E. coli K12 were added to determine the ability of the macrophages to kill the bacteria. In a final experiment, mice were intravenously infected with E. coli to assess the ability of stressed and nonstressed mice to clear the bacteria from the blood and the spleen. Results: Both TLR2 and TLR4 expressions on splenic CD11b+ macrophages were significantly increased during SDR as demonstrated by a significant increase in the fluorescence intensity of anti-TLR2 and anti-TLR4 staining. In addition, splenic macrophages from stressed mice killed over 60% of the E. coli after 90 min in culture, whereas control cells killed less than 10 % of the bacteria. Moreover, the number of E. coli in the blood and spleens of stressed mice was significantly lower than in nonstressed controls. Conclusions: Repeated social defeat significantly increases microbicidal activity of splenic macrophages both in vitro and in vivo. Although the mechanisms through which this enhancement occurs are not yet defined, it is likely that stress-enhanced TLR expression and signaling are involved. doi:10.1016/j.bbi.2006.04.006
Obesity and altered stress responsiveness in women with polycystic ovary syndrome: Implications for the long-term cardiovascular and diabetes risks associated with the diagnosis? Sven Benson a, Petra C. Arck b, Nadja Rifaie a, Katja Pleger a, Susanne Tan c, Susanne Hahn d, Onno E. Janssen c, Sigrid Elsenbruch a a
Department of Medical Psychology, University of Essen Medical School, Germany b Biomedical Research Center, Department of Internal Medicine, Charite-University Medicine, Berlin, Germany c Division of Endocrinology, Department of Medicine, University Hospital of Essen Medical School, Germany d Endokrinologikum Ruhr, Center for endocrine and metabolic diseases, Bochum, Germany Background: Obesity in combination with insulin resistance and hyperandrogenism are amongst the characteristic features of the polycystic ovary syndrome (PCOS), affecting about 6% of women of reproductive age. A markedly increased proportion of PCOS women meet the diagnostic criteria for the metabolic syndrome as well as for type 2 diabetes at a relatively young age. Accordingly, the long-term risk of cardiovascular disease is thought to be substantially increased. Although there is evidence to
the effect of acute (60 min) restraint administered immediately before spared nerve injury (SNI) on neuropathic pain. Allodynia was assessed before and 24 h after a single period of restraint and was found to be similar between WT and KO mice. However, 1, 3, 5, and 7 days after SNI, allodynia (assessed by von Frey monofilaments) in the hindpaw ipsilateral to the injury was significantly enhanced in stressed KO mice as compared to stressed WT and non-stressed mice. In addition, mechanical allodynia in the hindpaw contralateral to the injury was enhanced in stressed KO mice compared to stressed WT mice. Cold allodynia (assessed by acetone application) was signficantly increased for stressed KO mice on days 3, 5, and 7 post-SNI in the hindpaw ipsilateral to the injury and overall post-SNI in the hindpaw contralateral to the injury compared to non-stressed KO mice. In summary, male CX3CR1-/- mice exhibit enhanced ipsilateral mechanical allodynia with enhanced mirror image pain following SNI compared to wild-type mice. These effects were potentiated by stress. These data suggest that the absence of the CX3CR1 does not confer protection from the onset of allodynia after peripheral nerve injury. However, other factors (e.g., corticosterone) produced as a result of stress or concomitant injury may enhance neuropathic pain. doi:10.1016/j.bbi.2006.04.005
Toll-like receptor expression and bactericidal activity are increased in splenic macrophages from socially stressed mice Michael T. Bailey a, Harald Engler a, David A. Padgett b, John F. Sheridan b a
Section of Oral Biology, College of Dentistry, The Institute for Behavioral Medicine Research, The Ohio State University, Columbus, OH, USA b Department of Molecular Virology, Immunology and Medical Genetics, The Institute for Behavioral Medicine Research, The Ohio State University, Columbus, OH, USA Background: Phagocytes of the innate immune system represent a first line of defense against invading microbes. Thus, altering the function of these cells can have a profound impact on the course of an infectious challenge. In mice, repeated social defeat significantly alters macrophage functioning by enhancing cytokine production upon stimulation with lipopolysaccharide, suggesting that the macrophages are primed by exposure to the stressor. Because priming is likely to be associated with enhanced toll-like receptor (TLR) expression and bactericidal activity, it was hypothesized that repeated social defeat would increase the expression of TLRs and the ability of splenic macrophages to kill Escherichia coli. Methods: Mice were exposed to social disruption (SDR) stress, by placing an intruder mouse into the cage of five resident mice for 2 h on six consecutive days. On the day following the last cycle, single cell suspensions were created
e3
from the spleen. To determine the impact of SDR on TLR2 and TLR4 expression, magnetic beads ligated to anti-CD11b+ antibodies were used to enrich cultures for CD11b+ cells. Flow cytometry was then used to quantify TLR2 and TLR4 surface expression. In a follow up experiment, bactericidal activity was assessed in cultures standardized by flow cytometry to contain 5 · 104 CD11b+ macrophages. Live E. coli K12 were added to determine the ability of the macrophages to kill the bacteria. In a final experiment, mice were intravenously infected with E. coli to assess the ability of stressed and nonstressed mice to clear the bacteria from the blood and the spleen. Results: Both TLR2 and TLR4 expressions on splenic CD11b+ macrophages were significantly increased during SDR as demonstrated by a significant increase in the fluorescence intensity of anti-TLR2 and anti-TLR4 staining. In addition, splenic macrophages from stressed mice killed over 60% of the E. coli after 90 min in culture, whereas control cells killed less than 10 % of the bacteria. Moreover, the number of E. coli in the blood and spleens of stressed mice was significantly lower than in nonstressed controls. Conclusions: Repeated social defeat significantly increases microbicidal activity of splenic macrophages both in vitro and in vivo. Although the mechanisms through which this enhancement occurs are not yet defined, it is likely that stress-enhanced TLR expression and signaling are involved. doi:10.1016/j.bbi.2006.04.006
Obesity and altered stress responsiveness in women with polycystic ovary syndrome: Implications for the long-term cardiovascular and diabetes risks associated with the diagnosis? Sven Benson a, Petra C. Arck b, Nadja Rifaie a, Katja Pleger a, Susanne Tan c, Susanne Hahn d, Onno E. Janssen c, Sigrid Elsenbruch a a
Department of Medical Psychology, University of Essen Medical School, Germany b Biomedical Research Center, Department of Internal Medicine, Charite-University Medicine, Berlin, Germany c Division of Endocrinology, Department of Medicine, University Hospital of Essen Medical School, Germany d Endokrinologikum Ruhr, Center for endocrine and metabolic diseases, Bochum, Germany Background: Obesity in combination with insulin resistance and hyperandrogenism are amongst the characteristic features of the polycystic ovary syndrome (PCOS), affecting about 6% of women of reproductive age. A markedly increased proportion of PCOS women meet the diagnostic criteria for the metabolic syndrome as well as for type 2 diabetes at a relatively young age. Accordingly, the long-term risk of cardiovascular disease is thought to be substantially increased. Although there is evidence to