{"id":{"repo_id":"goteborg","oai_identifier":"oai:gupea.ub.gu.se:2077/21944"},"canonical_url":"https://search.dev.ndltd.org/etd/goteborg/oai:gupea.ub.gu.se:2077/21944","repository":{"repo_id":"goteborg","name":"Gothenburg University","base_url":"https://gupea.ub.gu.se/oai/request"},"display":{"title":"Modulatory role of IL-17 in airway inflammation","abstract":"IL-17 orchestrates the accumulation of neutrophils to sites of infection and the release of microbicidal substances, and therefore plays a critical role in the innate immune response to infection. IL-17 is also involved in certain chronic inflammatory diseases in which dysfunctional control of neutrophil accumulation and turnover constitutes an important pathogenic factor. This pro-inflammatory potential of IL-17 in host defence and in inflammatory diseases has been studied extensively. However, there is now also published evidence that IL-17 has more complex actions, including inflammation-resolving potential under certain conditions. With this in mind, the aims of this thesis were to investigate endogenous and exogenous methods to regulate the production of IL-17 and to elucidate the role that IL-17 plays in resolving ongoing inflammation. More specifically, we looked at whether the cells in the lung produce IL-17 after exposure to lipopolysaccharide (LPS) from the Gram-negative Escherichia coli bacteria, and whether anti-inflammatory pharmacotherapies could be used to regulate the production of IL-17 in these cells. We also examined whether IL-17 contributes to neutrophil turnover through the regulation of macrophage phagocytosis of apoptotic neutrophils. Finally, we investigated whether IL-17 down-regulates the release of the upstream regulator IL-23. We found that LPS induced sustained IL-17 production and release from T cells that reside in lung tissue and that are recruited to the bronchoalveolar space in a mouse model of acute inflammation in vivo. In addition, population of cells other than T cells contributed to IL-17 production in the lung tissues and in the bronchoalveolar space. LPS-induced IL-17 production from T cells in lung tissues and in the bronchoalveolar space was inhibited by the anti-inflammatory drug dexamethasone. Furthermore, we found that IL-17 stimulated macrophage phagocytosis of apoptotic neutrophils and particles, and induced neutrophil apoptosis in an in vitro study on isolated murine and human cells. Finally, we found that that IL-17 inhibited the release of the upstream regulator IL-23, both in the bronchoalveolar space in mice in vivo and in isolated human cells of the monocyte lineage. A major finding is that the production of IL-17 can be regulated exogenously by anti-inflammatory drugs and endogenously by an IL-17-induced feedback loop, which, in turn, may protect against excessive, IL-23-induced IL-17 signalling. In addition, we demonstrate that IL-17 has both pro-inflammatory and inflammation-resolving actions; IL-17 accumulates neutrophils after stimulation with LPS, while it also induces the phagocytosis of apoptotic neutrophils, thereby controlling the total turnover of neutrophils. That IL-17 induces the apoptosis of neutrophils and increases the phagocytosis of these cells indicates a potentially valuable strategy to mitigate conditions in which necrotic neutrophils are an important contributor to severe and sometimes life-threatening conditions, such as chronic lung allograft rejection and acute respiratory distress syndrome.","abstract_html":"IL-17 orchestrates the accumulation of neutrophils to sites of infection and the release of microbicidal substances, and therefore plays a critical role in the innate immune response to infection. IL-17 is also involved in certain chronic inflammatory diseases in which dysfunctional control of neutrophil accumulation and turnover constitutes an important pathogenic factor. This pro-inflammatory potential of IL-17 in host defence and in inflammatory diseases has been studied extensively. However, there is now also published evidence that IL-17 has more complex actions, including inflammation-resolving potential under certain conditions. With this in mind, the aims of this thesis were to investigate endogenous and exogenous methods to regulate the production of IL-17 and to elucidate the role that IL-17 plays in resolving ongoing inflammation. More specifically, we looked at whether the cells in the lung produce IL-17 after exposure to lipopolysaccharide (LPS) from the Gram-negative Escherichia coli bacteria, and whether anti-inflammatory pharmacotherapies could be used to regulate the production of IL-17 in these cells. We also examined whether IL-17 contributes to neutrophil turnover through the regulation of macrophage phagocytosis of apoptotic neutrophils. Finally, we investigated whether IL-17 down-regulates the release of the upstream regulator IL-23. We found that LPS induced sustained IL-17 production and release from T cells that reside in lung tissue and that are recruited to the bronchoalveolar space in a mouse model of acute inflammation in vivo. In addition, population of cells other than T cells contributed to IL-17 production in the lung tissues and in the bronchoalveolar space. LPS-induced IL-17 production from T cells in lung tissues and in the bronchoalveolar space was inhibited by the anti-inflammatory drug dexamethasone. Furthermore, we found that IL-17 stimulated macrophage phagocytosis of apoptotic neutrophils and particles, and induced neutrophil apoptosis in an in vitro study on isolated murine and human cells. Finally, we found that that IL-17 inhibited the release of the upstream regulator IL-23, both in the bronchoalveolar space in mice in vivo and in isolated human cells of the monocyte lineage. A major finding is that the production of IL-17 can be regulated exogenously by anti-inflammatory drugs and endogenously by an IL-17-induced feedback loop, which, in turn, may protect against excessive, IL-23-induced IL-17 signalling. In addition, we demonstrate that IL-17 has both pro-inflammatory and inflammation-resolving actions; IL-17 accumulates neutrophils after stimulation with LPS, while it also induces the phagocytosis of apoptotic neutrophils, thereby controlling the total turnover of neutrophils. That IL-17 induces the apoptosis of neutrophils and increases the phagocytosis of these cells indicates a potentially valuable strategy to mitigate conditions in which necrotic neutrophils are an important contributor to severe and sometimes life-threatening conditions, such as chronic lung allograft rejection and acute respiratory distress syndrome.","abstract_has_math":false,"creators":["Silverpil, Elin"],"institution":null,"degree_name":null,"degree_level":null,"degree_discipline":null,"degree_department":null,"school":null,"contributors":[],"advisors":[],"committee_chairs":[],"committee_members":[],"year":2010,"date_issued":"2010-05-11T07:23:26Z","date_published":"2010-05-11T07:23:26Z","updated_at":"2026-08-21T22:21:56Z","subjects":["Respiratory medicine","Lung","IL-17","IL-23","Macrophages","Neutrophils","T cells","Apoptosis","Phagocytosis","Airways"],"languages":["eng"],"rights":[],"rights_urls":[],"identifier_entries":[]},"links":{"outbound_url":"http://hdl.handle.net/2077/21944","outbound_label":"Handle","outbound_source":"dc:identifier.uri"},"source_record":{"url":"https://gupea.ub.gu.se/oai/request?verb=GetRecord&metadataPrefix=dim&identifier=oai%3Agupea.ub.gu.se%3A2077%2F21944","prefix":"dim"},"metadata_groups":[{"id":"people","label":"People","entries":[{"key":"dc:creator","label":"Author","values":["Silverpil, Elin"]}]},{"id":"academic_context","label":"Academic Context","entries":[{"key":"dc:date.accessioned","label":"Dc Date Accessioned","values":["2010-05-11T07:23:26Z"]},{"key":"dc:date.available","label":"Dc Date Available","values":["2010-05-11T07:23:26Z"]},{"key":"dc:date.issued","label":"Date","values":["2010-05-11T07:23:26Z"]},{"key":"dc:type","label":"Dc Type","values":["text"]}]},{"id":"subjects_keywords","label":"Subjects and Keywords","entries":[{"key":"dc:subject","label":"Dc Subject","values":["Respiratory medicine","Lung","IL-17","IL-23","Macrophages","Neutrophils","T cells","Apoptosis","Phagocytosis","Airways"]}]},{"id":"language_rights","label":"Language and Rights","entries":[{"key":"dc:language.iso","label":"Language (ISO)","values":["eng"]}]},{"id":"identifiers","label":"Identifiers","entries":[{"key":"dc:identifier.uri","label":"Identifier URI","values":["http://hdl.handle.net/2077/21944"]}]},{"id":"additional","label":"Additional Metadata","entries":[{"key":"dc:description.abstract","label":"Abstract","values":["IL-17 orchestrates the accumulation of neutrophils to sites of infection and the release of microbicidal substances, and therefore plays a critical role in the innate immune response to infection. IL-17 is also involved in certain chronic inflammatory diseases in which dysfunctional control of neutrophil accumulation and turnover constitutes an important pathogenic factor. This pro-inflammatory potential of IL-17 in host defence and in inflammatory diseases has been studied extensively. However, there is now also published evidence that IL-17 has more complex actions, including inflammation-resolving potential under certain conditions. With this in mind, the aims of this thesis were to investigate endogenous and exogenous methods to regulate the production of IL-17 and to elucidate the role that IL-17 plays in resolving ongoing inflammation. More specifically, we looked at whether the cells in the lung produce IL-17 after exposure to lipopolysaccharide (LPS) from the Gram-negative Escherichia coli bacteria, and whether anti-inflammatory pharmacotherapies could be used to regulate the production of IL-17 in these cells. We also examined whether IL-17 contributes to neutrophil turnover through the regulation of macrophage phagocytosis of apoptotic neutrophils. Finally, we investigated whether IL-17 down-regulates the release of the upstream regulator IL-23. We found that LPS induced sustained IL-17 production and release from T cells that reside in lung tissue and that are recruited to the bronchoalveolar space in a mouse model of acute inflammation in vivo. In addition, population of cells other than T cells contributed to IL-17 production in the lung tissues and in the bronchoalveolar space. LPS-induced IL-17 production from T cells in lung tissues and in the bronchoalveolar space was inhibited by the anti-inflammatory drug dexamethasone. Furthermore, we found that IL-17 stimulated macrophage phagocytosis of apoptotic neutrophils and particles, and induced neutrophil apoptosis in an in vitro study on isolated murine and human cells. Finally, we found that that IL-17 inhibited the release of the upstream regulator IL-23, both in the bronchoalveolar space in mice in vivo and in isolated human cells of the monocyte lineage. A major finding is that the production of IL-17 can be regulated exogenously by anti-inflammatory drugs and endogenously by an IL-17-induced feedback loop, which, in turn, may protect against excessive, IL-23-induced IL-17 signalling. In addition, we demonstrate that IL-17 has both pro-inflammatory and inflammation-resolving actions; IL-17 accumulates neutrophils after stimulation with LPS, while it also induces the phagocytosis of apoptotic neutrophils, thereby controlling the total turnover of neutrophils. That IL-17 induces the apoptosis of neutrophils and increases the phagocytosis of these cells indicates a potentially valuable strategy to mitigate conditions in which necrotic neutrophils are an important contributor to severe and sometimes life-threatening conditions, such as chronic lung allograft rejection and acute respiratory distress syndrome."]},{"key":"dc:title","label":"Title","values":["Modulatory role of IL-17 in airway inflammation"]}]}],"canonical_facts":{"dc:creator":["Silverpil, Elin"],"dc:date.accessioned":["2010-05-11T07:23:26Z"],"dc:date.available":["2010-05-11T07:23:26Z"],"dc:date.issued":["2010-05-11T07:23:26Z"],"dc:description.abstract":["IL-17 orchestrates the accumulation of neutrophils to sites of infection and the release of microbicidal substances, and therefore plays a critical role in the innate immune response to infection. IL-17 is also involved in certain chronic inflammatory diseases in which dysfunctional control of neutrophil accumulation and turnover constitutes an important pathogenic factor. This pro-inflammatory potential of IL-17 in host defence and in inflammatory diseases has been studied extensively. However, there is now also published evidence that IL-17 has more complex actions, including inflammation-resolving potential under certain conditions. With this in mind, the aims of this thesis were to investigate endogenous and exogenous methods to regulate the production of IL-17 and to elucidate the role that IL-17 plays in resolving ongoing inflammation. More specifically, we looked at whether the cells in the lung produce IL-17 after exposure to lipopolysaccharide (LPS) from the Gram-negative Escherichia coli bacteria, and whether anti-inflammatory pharmacotherapies could be used to regulate the production of IL-17 in these cells. We also examined whether IL-17 contributes to neutrophil turnover through the regulation of macrophage phagocytosis of apoptotic neutrophils. Finally, we investigated whether IL-17 down-regulates the release of the upstream regulator IL-23. We found that LPS induced sustained IL-17 production and release from T cells that reside in lung tissue and that are recruited to the bronchoalveolar space in a mouse model of acute inflammation in vivo. In addition, population of cells other than T cells contributed to IL-17 production in the lung tissues and in the bronchoalveolar space. LPS-induced IL-17 production from T cells in lung tissues and in the bronchoalveolar space was inhibited by the anti-inflammatory drug dexamethasone. Furthermore, we found that IL-17 stimulated macrophage phagocytosis of apoptotic neutrophils and particles, and induced neutrophil apoptosis in an in vitro study on isolated murine and human cells. Finally, we found that that IL-17 inhibited the release of the upstream regulator IL-23, both in the bronchoalveolar space in mice in vivo and in isolated human cells of the monocyte lineage. A major finding is that the production of IL-17 can be regulated exogenously by anti-inflammatory drugs and endogenously by an IL-17-induced feedback loop, which, in turn, may protect against excessive, IL-23-induced IL-17 signalling. In addition, we demonstrate that IL-17 has both pro-inflammatory and inflammation-resolving actions; IL-17 accumulates neutrophils after stimulation with LPS, while it also induces the phagocytosis of apoptotic neutrophils, thereby controlling the total turnover of neutrophils. That IL-17 induces the apoptosis of neutrophils and increases the phagocytosis of these cells indicates a potentially valuable strategy to mitigate conditions in which necrotic neutrophils are an important contributor to severe and sometimes life-threatening conditions, such as chronic lung allograft rejection and acute respiratory distress syndrome."],"dc:identifier.uri":["http://hdl.handle.net/2077/21944"],"dc:language.iso":["eng"],"dc:subject":["Respiratory medicine","Lung","IL-17","IL-23","Macrophages","Neutrophils","T cells","Apoptosis","Phagocytosis","Airways"],"dc:title":["Modulatory role of IL-17 in airway inflammation"],"dc:type":["text"]},"updated_at":"2026-08-21T22:21:56Z"}