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We are analyzing https://link.springer.com/article/10.1186/cc13970.

Title:
Receptor-interacting protein kinase 3 deficiency inhibits immune cell infiltration and attenuates organ injury in sepsis | Critical Care
Description:
Introduction Sepsis is defined as a systemic hyper-inflammatory immune response, with a subsequent immune-suppressive phase, which leads to multiple organ dysfunction and late lethality. Receptor-interacting protein kinase 3 (RIPK3)-dependent necrosis is implicated in driving tumor necrosis factor alpha (TNF-α)- and sepsis-induced mortality in mice. However, it is unknown if RIPK3 deficiency has any impact on immune cell trafficking, which contributes to organ damage in sepsis. Methods To study this, male wild-type (WT) and RIPK3-deficient (Ripk3 -/-) mice on C57BL/6 background were subjected to sham operation or cecal ligation and puncture (CLP)-induced sepsis. Blood and tissue samples were collected 20 hours post-CLP for various measurements. Results In our severe sepsis model, the mean survival time of Ripk3 -/- mice was significantly extended to 68 hours compared to 41 hours for WT mice. Ripk3 -/- mice had significantly decreased plasma levels of TNF-α and IL-6 and organ injury markers compared to WT mice post-CLP. In the lungs, Ripk3 -/- mice preserved better integrity of microscopic structure with reduced apoptosis, and decreased levels of IL-6, macrophage inflammatory protein (MIP)-2 and keratinocyte-derived chemokine (KC), compared to WT. In the liver, the levels of MIP-1, MIP-2 and KC were also decreased in septic Ripk3 -/- mice. Particularly, the total number of neutrophils in the lungs and liver of Ripk3 -/- mice decreased by 59.9% and 66.7%, respectively, compared to WT mice post-CLP. In addition, the number of natural killer (NK) and CD8T cells in the liver decreased by 64.8% and 53.4%, respectively, in Ripk3 -/- mice compared to WT mice post-sepsis. Conclusions Our data suggest that RIPK3 deficiency modestly protected from CLP-induced severe sepsis and altered the immune cell trafficking in an organ-specific manner attenuating organ injury. Thus, RIPK3 acts as a detrimental factor in contributing to the organ deterioration in sepsis.
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Keywords {🔍}

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Questions {❓}

  • Ayala A, Evans TA, Chaudry IH: Does hepatocellular injury in sepsis involve apoptosis?

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WebPage:
      mainEntity:
         headline:Receptor-interacting protein kinase 3 deficiency inhibits immune cell infiltration and attenuates organ injury in sepsis
         description:Sepsis is defined as a systemic hyper-inflammatory immune response, with a subsequent immune-suppressive phase, which leads to multiple organ dysfunction and late lethality. Receptor-interacting protein kinase 3 (RIPK3)-dependent necrosis is implicated in driving tumor necrosis factor alpha (TNF-α)- and sepsis-induced mortality in mice. However, it is unknown if RIPK3 deficiency has any impact on immune cell trafficking, which contributes to organ damage in sepsis. To study this, male wild-type (WT) and RIPK3-deficient (Ripk3 -/-) mice on C57BL/6 background were subjected to sham operation or cecal ligation and puncture (CLP)-induced sepsis. Blood and tissue samples were collected 20 hours post-CLP for various measurements. In our severe sepsis model, the mean survival time of Ripk3 -/- mice was significantly extended to 68 hours compared to 41 hours for WT mice. Ripk3 -/- mice had significantly decreased plasma levels of TNF-α and IL-6 and organ injury markers compared to WT mice post-CLP. In the lungs, Ripk3 -/- mice preserved better integrity of microscopic structure with reduced apoptosis, and decreased levels of IL-6, macrophage inflammatory protein (MIP)-2 and keratinocyte-derived chemokine (KC), compared to WT. In the liver, the levels of MIP-1, MIP-2 and KC were also decreased in septic Ripk3 -/- mice. Particularly, the total number of neutrophils in the lungs and liver of Ripk3 -/- mice decreased by 59.9% and 66.7%, respectively, compared to WT mice post-CLP. In addition, the number of natural killer (NK) and CD8T cells in the liver decreased by 64.8% and 53.4%, respectively, in Ripk3 -/- mice compared to WT mice post-sepsis. Our data suggest that RIPK3 deficiency modestly protected from CLP-induced severe sepsis and altered the immune cell trafficking in an organ-specific manner attenuating organ injury. Thus, RIPK3 acts as a detrimental factor in contributing to the organ deterioration in sepsis.
         datePublished:2014-07-04T00:00:00Z
         dateModified:2014-07-04T00:00:00Z
         pageStart:1
         pageEnd:13
         license:http://creativecommons.org/licenses/by/4.0/
         sameAs:https://doi.org/10.1186/cc13970
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            Natural Killer Cell
            Wild Type Mouse
            Acute Lung Injury
            Septic Mouse
            Polymicrobial Sepsis
            Intensive / Critical Care Medicine
            Emergency Medicine
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      headline:Receptor-interacting protein kinase 3 deficiency inhibits immune cell infiltration and attenuates organ injury in sepsis
      description:Sepsis is defined as a systemic hyper-inflammatory immune response, with a subsequent immune-suppressive phase, which leads to multiple organ dysfunction and late lethality. Receptor-interacting protein kinase 3 (RIPK3)-dependent necrosis is implicated in driving tumor necrosis factor alpha (TNF-α)- and sepsis-induced mortality in mice. However, it is unknown if RIPK3 deficiency has any impact on immune cell trafficking, which contributes to organ damage in sepsis. To study this, male wild-type (WT) and RIPK3-deficient (Ripk3 -/-) mice on C57BL/6 background were subjected to sham operation or cecal ligation and puncture (CLP)-induced sepsis. Blood and tissue samples were collected 20 hours post-CLP for various measurements. In our severe sepsis model, the mean survival time of Ripk3 -/- mice was significantly extended to 68 hours compared to 41 hours for WT mice. Ripk3 -/- mice had significantly decreased plasma levels of TNF-α and IL-6 and organ injury markers compared to WT mice post-CLP. In the lungs, Ripk3 -/- mice preserved better integrity of microscopic structure with reduced apoptosis, and decreased levels of IL-6, macrophage inflammatory protein (MIP)-2 and keratinocyte-derived chemokine (KC), compared to WT. In the liver, the levels of MIP-1, MIP-2 and KC were also decreased in septic Ripk3 -/- mice. Particularly, the total number of neutrophils in the lungs and liver of Ripk3 -/- mice decreased by 59.9% and 66.7%, respectively, compared to WT mice post-CLP. In addition, the number of natural killer (NK) and CD8T cells in the liver decreased by 64.8% and 53.4%, respectively, in Ripk3 -/- mice compared to WT mice post-sepsis. Our data suggest that RIPK3 deficiency modestly protected from CLP-induced severe sepsis and altered the immune cell trafficking in an organ-specific manner attenuating organ injury. Thus, RIPK3 acts as a detrimental factor in contributing to the organ deterioration in sepsis.
      datePublished:2014-07-04T00:00:00Z
      dateModified:2014-07-04T00:00:00Z
      pageStart:1
      pageEnd:13
      license:http://creativecommons.org/licenses/by/4.0/
      sameAs:https://doi.org/10.1186/cc13970
      keywords:
         Natural Killer Cell
         Wild Type Mouse
         Acute Lung Injury
         Septic Mouse
         Polymicrobial Sepsis
         Intensive / Critical Care Medicine
         Emergency Medicine
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                     name:Department of Surgery II, Tokyo Women’s Medical University, Tokyo, Japan
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                     name:Center for Translational Research, The Feinstein Institute for Medical Research, Manhasset, USA
                     type:PostalAddress
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                     type:PostalAddress
                  type:Organization
            type:Person
            name:Ping Wang
            affiliation:
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            name:The Feinstein Institute for Medical Research
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            address:
               name:Department of Surgery, Hofstra North Shore-LIJ School of Medicine, Manhasset, USA
               type:PostalAddress
            type:Organization
      name:Zhimin Wang
      affiliation:
            name:The Feinstein Institute for Medical Research
            address:
               name:Center for Translational Research, The Feinstein Institute for Medical Research, Manhasset, USA
               type:PostalAddress
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            name:Hofstra North Shore-LIJ School of Medicine
            address:
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               type:PostalAddress
            type:Organization
      name:Ping Wang
      affiliation:
            name:The Feinstein Institute for Medical Research
            address:
               name:Center for Translational Research, The Feinstein Institute for Medical Research, Manhasset, USA
               type:PostalAddress
            type:Organization
            name:Hofstra North Shore-LIJ School of Medicine
            address:
               name:Department of Surgery, Hofstra North Shore-LIJ School of Medicine, Manhasset, USA
               type:PostalAddress
            type:Organization
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PostalAddress:
      name:Center for Translational Research, The Feinstein Institute for Medical Research, Manhasset, USA
      name:Department of Surgery, Hofstra North Shore-LIJ School of Medicine, Manhasset, USA
      name:Center for Translational Research, The Feinstein Institute for Medical Research, Manhasset, USA
      name:Department of Surgery, Hofstra North Shore-LIJ School of Medicine, Manhasset, USA
      name:Department of Surgery II, Tokyo Women’s Medical University, Tokyo, Japan
      name:Center for Translational Research, The Feinstein Institute for Medical Research, Manhasset, USA
      name:Department of Surgery, Hofstra North Shore-LIJ School of Medicine, Manhasset, USA
      name:Center for Translational Research, The Feinstein Institute for Medical Research, Manhasset, USA
      name:Department of Surgery, Hofstra North Shore-LIJ School of Medicine, Manhasset, USA
      name:Center for Translational Research, The Feinstein Institute for Medical Research, Manhasset, USA
      name:Department of Surgery, Hofstra North Shore-LIJ School of Medicine, Manhasset, USA

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