{"id":{"repo_id":"ohiolink","oai_identifier":"oai:etd.ohiolink.edu:osu1365174635"},"canonical_url":"https://search.dev.ndltd.org/etd/ohiolink/oai:etd.ohiolink.edu:osu1365174635","repository":{"repo_id":"ohiolink","name":"OhioLINK","base_url":"https://etd.ohiolink.edu/acprod/odb_etd/ws/oai/oai"},"display":{"title":"The role of mitochondrial DAMPs on the inflammatory response in an <i>in vitro</i> model of canine SIRS","abstract":"SIRS and sepsis are common systemic inflammatory conditions that affect both dogs and humans. Despite advances in optimizing supportive care, case fatality levels for these syndromes unfortunately remain high in a large subset of patients. Novel therapies are desperately needed in an attempt to mitigate the inflammatory response and improve patient outcomes in these all-too-common conditions.Endogenous danger signals from damaged cells trigger inflammatory responses in sepsis and conditions leading to SIRS. Much work has recently been performed that demonstrates the importance of signals from mitochondrial fragments – termed damage-associated molecular patterns or DAMPs – in helping to initiate and perpetuate this inflammatory response. These findings have yet to be investigated in a large animal model such as dogs. Given the similarities between dogs and humans, and questions regarding the usefulness of rodent models in modeling human disease, we have developed a preliminary <i>in vitro</i> model system to investigate the effects of mitochondrial DAMPs (as well as other DAMPs) in dogs.Our model system relies primarily on the use of splenocytes, which constitute a mixed population of inflammatory cells that is likely to mimic <i>in vivo</i> conditions and has been used by others to assess responses in models of SIRS and sepsis. Additionally, we employed dendritic cells in our model, as these antigen presenting cells are first responders to inflammatory stimuli and comprise an important subset of the splenocyte population.This study demonstrates the pro-inflammatory nature of mitochondrial DAMPs in dogs. Specifically, this work shows that mitochondrial DAMPs increase the production of the cytokine TNF-a while having little effect on IL-1ß, IL-6, IFN-a, or the expression of cell surface receptors MHC class II or CD80. Highly purified recombinant HMGB1 had no effects in our model systems. This study also validates the utility of an <i>in vitro</i> splenocyte assay to evaluate DAMP-induced inflammation in dogs. Both ELISA and qRT-PCR were useful screening methods for assessing the inflammatory response.","abstract_html":"SIRS and sepsis are common systemic inflammatory conditions that affect both dogs and humans. Despite advances in optimizing supportive care, case fatality levels for these syndromes unfortunately remain high in a large subset of patients. Novel therapies are desperately needed in an attempt to mitigate the inflammatory response and improve patient outcomes in these all-too-common conditions.Endogenous danger signals from damaged cells trigger inflammatory responses in sepsis and conditions leading to SIRS. Much work has recently been performed that demonstrates the importance of signals from mitochondrial fragments – termed damage-associated molecular patterns or DAMPs – in helping to initiate and perpetuate this inflammatory response. These findings have yet to be investigated in a large animal model such as dogs. Given the similarities between dogs and humans, and questions regarding the usefulness of rodent models in modeling human disease, we have developed a preliminary &lt;i&gt;in vitro&lt;/i&gt; model system to investigate the effects of mitochondrial DAMPs (as well as other DAMPs) in dogs.Our model system relies primarily on the use of splenocytes, which constitute a mixed population of inflammatory cells that is likely to mimic &lt;i&gt;in vivo&lt;/i&gt; conditions and has been used by others to assess responses in models of SIRS and sepsis. Additionally, we employed dendritic cells in our model, as these antigen presenting cells are first responders to inflammatory stimuli and comprise an important subset of the splenocyte population.This study demonstrates the pro-inflammatory nature of mitochondrial DAMPs in dogs. Specifically, this work shows that mitochondrial DAMPs increase the production of the cytokine TNF-a while having little effect on IL-1ß, IL-6, IFN-a, or the expression of cell surface receptors MHC class II or CD80. Highly purified recombinant HMGB1 had no effects in our model systems. This study also validates the utility of an &lt;i&gt;in vitro&lt;/i&gt; splenocyte assay to evaluate DAMP-induced inflammation in dogs. Both ELISA and qRT-PCR were useful screening methods for assessing the inflammatory response.","abstract_has_math":false,"creators":["Friedenberg, Steven Gene"],"institution":"The Ohio State University","degree_name":"Master of Science","degree_level":"masters","degree_discipline":"Veterinary Clinical Sciences","degree_department":null,"school":null,"contributors":["Papenfuss, Tracey"],"advisors":[],"committee_chairs":[],"committee_members":[],"year":2013,"date_issued":"2013-07-12","date_published":"2013-07-12","updated_at":"2026-07-24T03:37:01Z","subjects":["Animal Sciences","Animals","Animal Diseases","Immunology"],"languages":["English"],"rights":["unrestricted","This thesis or dissertation is protected by copyright: all rights reserved. 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Much work has recently been performed that demonstrates the importance of signals from mitochondrial fragments – termed damage-associated molecular patterns or DAMPs – in helping to initiate and perpetuate this inflammatory response. These findings have yet to be investigated in a large animal model such as dogs. Given the similarities between dogs and humans, and questions regarding the usefulness of rodent models in modeling human disease, we have developed a preliminary <i>in vitro</i> model system to investigate the effects of mitochondrial DAMPs (as well as other DAMPs) in dogs.Our model system relies primarily on the use of splenocytes, which constitute a mixed population of inflammatory cells that is likely to mimic <i>in vivo</i> conditions and has been used by others to assess responses in models of SIRS and sepsis. Additionally, we employed dendritic cells in our model, as these antigen presenting cells are first responders to inflammatory stimuli and comprise an important subset of the splenocyte population.This study demonstrates the pro-inflammatory nature of mitochondrial DAMPs in dogs. Specifically, this work shows that mitochondrial DAMPs increase the production of the cytokine TNF-a while having little effect on IL-1ß, IL-6, IFN-a, or the expression of cell surface receptors MHC class II or CD80. Highly purified recombinant HMGB1 had no effects in our model systems. This study also validates the utility of an <i>in vitro</i> splenocyte assay to evaluate DAMP-induced inflammation in dogs. Both ELISA and qRT-PCR were useful screening methods for assessing the inflammatory response."]},{"key":"dc:format","label":"Dc Format","values":["application/pdf","p.123","15.34 MB"]},{"key":"dc:title","label":"Title","values":["The role of mitochondrial DAMPs on the inflammatory response in an <i>in vitro</i> model of canine SIRS"]}]}],"canonical_facts":{"dc:contributor":["Papenfuss, Tracey"],"dc:creator":["Friedenberg, Steven Gene"],"dc:date":["2013-07-12"],"dc:description":["SIRS and sepsis are common systemic inflammatory conditions that affect both dogs and humans. Despite advances in optimizing supportive care, case fatality levels for these syndromes unfortunately remain high in a large subset of patients. Novel therapies are desperately needed in an attempt to mitigate the inflammatory response and improve patient outcomes in these all-too-common conditions.Endogenous danger signals from damaged cells trigger inflammatory responses in sepsis and conditions leading to SIRS. Much work has recently been performed that demonstrates the importance of signals from mitochondrial fragments – termed damage-associated molecular patterns or DAMPs – in helping to initiate and perpetuate this inflammatory response. These findings have yet to be investigated in a large animal model such as dogs. Given the similarities between dogs and humans, and questions regarding the usefulness of rodent models in modeling human disease, we have developed a preliminary <i>in vitro</i> model system to investigate the effects of mitochondrial DAMPs (as well as other DAMPs) in dogs.Our model system relies primarily on the use of splenocytes, which constitute a mixed population of inflammatory cells that is likely to mimic <i>in vivo</i> conditions and has been used by others to assess responses in models of SIRS and sepsis. Additionally, we employed dendritic cells in our model, as these antigen presenting cells are first responders to inflammatory stimuli and comprise an important subset of the splenocyte population.This study demonstrates the pro-inflammatory nature of mitochondrial DAMPs in dogs. Specifically, this work shows that mitochondrial DAMPs increase the production of the cytokine TNF-a while having little effect on IL-1ß, IL-6, IFN-a, or the expression of cell surface receptors MHC class II or CD80. Highly purified recombinant HMGB1 had no effects in our model systems. This study also validates the utility of an <i>in vitro</i> splenocyte assay to evaluate DAMP-induced inflammation in dogs. 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