{"id":{"repo_id":"ottawa-retro","oai_identifier":"oai:ruor.uottawa.ca:10393/37331"},"canonical_url":"https://search.dev.ndltd.org/etd/ottawa-retro/oai:ruor.uottawa.ca:10393/37331","repository":{"repo_id":"ottawa-retro","name":"University of Ottawa","base_url":"https://ruor.uottawa.ca/server/oai/request"},"display":{"title":"Molecular Mechanisms Involved in Interleukin-1β Release by Macrophages Exposed to Metal Ions from Implantable Biomaterials","abstract":"Metal ions released from implantable biomaterials have been associated with adverse biological reactions that can limit implant longevity. Previous studies have shown that, in macrophages, Co2+, Cr3+, and Ni2+ can activate the NLR family pyrin domain-containing protein 3 (NLPR3) inflammasome, which is responsible for interleukin(IL)-1β production through caspase-1. Furthermore, these ions are known to induce oxidative stress, and inflammasome priming is known to involve nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB) signaling. However, the mechanisms of inflammasome activation by metal ions remain largely unknown. The objectives of this thesis were to determine if, in macrophages: 1. IL-1β release induced by metal ions is caspase-1-dependent; 2. caspase-1 activation and IL-1β release induced by metal ions are oxidative stress-dependent; and 3. IL-1β release induced by metal ions is NF-κB signaling pathway-dependent. Lipopolysaccharide (LPS)-primed murine bone-marrow-derived macrophages were exposed to Co2+, Cr3+, or Ni2+, with or without an inhibitor of caspase-1, oxidative stress, or NF-κB. Culture supernatants were analyzed for active caspase-1 (immunoblotting) and/or IL-1β (ELISA). Overall, results showed that while both Cr3+ and Ni2+ may be inducing inflammasome activation, Cr3+ is likely a more potent activator, acting through oxidative stress and the NF-κB signaling pathway. Further elucidation of the activation mechanisms may facilitate the development of therapeutic approaches to modulate the inflammatory response to metal ions, and thereby increase implant longevity.","abstract_html":"Metal ions released from implantable biomaterials have been associated with adverse biological reactions that can limit implant longevity. Previous studies have shown that, in macrophages, Co2+, Cr3+, and Ni2+ can activate the NLR family pyrin domain-containing protein 3 (NLPR3) inflammasome, which is responsible for interleukin(IL)-1β production through caspase-1. Furthermore, these ions are known to induce oxidative stress, and inflammasome priming is known to involve nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB) signaling. However, the mechanisms of inflammasome activation by metal ions remain largely unknown. The objectives of this thesis were to determine if, in macrophages: 1. IL-1β release induced by metal ions is caspase-1-dependent; 2. caspase-1 activation and IL-1β release induced by metal ions are oxidative stress-dependent; and 3. IL-1β release induced by metal ions is NF-κB signaling pathway-dependent. Lipopolysaccharide (LPS)-primed murine bone-marrow-derived macrophages were exposed to Co2+, Cr3+, or Ni2+, with or without an inhibitor of caspase-1, oxidative stress, or NF-κB. Culture supernatants were analyzed for active caspase-1 (immunoblotting) and/or IL-1β (ELISA). Overall, results showed that while both Cr3+ and Ni2+ may be inducing inflammasome activation, Cr3+ is likely a more potent activator, acting through oxidative stress and the NF-κB signaling pathway. Further elucidation of the activation mechanisms may facilitate the development of therapeutic approaches to modulate the inflammatory response to metal ions, and thereby increase implant longevity.","abstract_has_math":false,"creators":["Ferko, Maxime-Alexandre"],"institution":"Université d'Ottawa / University of Ottawa","degree_name":null,"degree_level":null,"degree_discipline":null,"degree_department":null,"school":null,"contributors":["Catelas, Isabelle"],"advisors":[],"committee_chairs":[],"committee_members":[],"year":2018,"date_issued":"2018-03-23T18:27:32Z","date_published":"2018-03-23T18:27:32Z","updated_at":"2026-07-24T03:39:42Z","subjects":["bioengineering","biomedical engineering","biomaterials","biocompatibility","orthopaedics","implants","metal alloys","metal ions","adverse tissue reactions","immune response","inflammation","molecular mechanisms","inflammasome activation","NLRP3","NALP3","macrophages","bone marrow-derived macrophages"],"languages":["en"],"rights":[],"rights_urls":[],"identifier_entries":[{"key":"dc:identifier","label":"Identifier","values":["http://dx.doi.org/10.20381/ruor-21603"],"render_values":[{"text":"http://dx.doi.org/10.20381/ruor-21603","href":"http://dx.doi.org/10.20381/ruor-21603","code":true}]}]},"links":{"outbound_url":"http://hdl.handle.net/10393/37331","outbound_label":"Handle","outbound_source":"dc:identifier"},"metadata_groups":[{"id":"people","label":"People","entries":[{"key":"dc:contributor","label":"Contributor","values":["Catelas, Isabelle"]},{"key":"dc:creator","label":"Author","values":["Ferko, Maxime-Alexandre"]}]},{"id":"academic_context","label":"Academic Context","entries":[{"key":"dc:date","label":"Dc Date","values":["2018-03-23T18:27:32Z","2018"]},{"key":"dc:publisher","label":"Institution","values":["Université d'Ottawa / University of Ottawa"]},{"key":"dc:type","label":"Dc Type","values":["Thesis"]}]},{"id":"subjects_keywords","label":"Subjects and Keywords","entries":[{"key":"dc:subject","label":"Dc Subject","values":["bioengineering","biomedical engineering","biomaterials","biocompatibility","orthopaedics","implants","metal alloys","metal ions","adverse tissue reactions","immune response","inflammation","molecular mechanisms","inflammasome activation","NLRP3","NALP3","macrophages","bone marrow-derived macrophages"]}]},{"id":"language_rights","label":"Language and Rights","entries":[{"key":"dc:language","label":"Dc Language","values":["en"]}]},{"id":"identifiers","label":"Identifiers","entries":[{"key":"dc:identifier","label":"Identifier","values":["http://hdl.handle.net/10393/37331","http://dx.doi.org/10.20381/ruor-21603"]}]},{"id":"additional","label":"Additional Metadata","entries":[{"key":"dc:description","label":"Description","values":["Metal ions released from implantable biomaterials have been associated with adverse biological reactions that can limit implant longevity. Previous studies have shown that, in macrophages, Co2+, Cr3+, and Ni2+ can activate the NLR family pyrin domain-containing protein 3 (NLPR3) inflammasome, which is responsible for interleukin(IL)-1β production through caspase-1. Furthermore, these ions are known to induce oxidative stress, and inflammasome priming is known to involve nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB) signaling. However, the mechanisms of inflammasome activation by metal ions remain largely unknown. The objectives of this thesis were to determine if, in macrophages: 1. IL-1β release induced by metal ions is caspase-1-dependent; 2. caspase-1 activation and IL-1β release induced by metal ions are oxidative stress-dependent; and 3. IL-1β release induced by metal ions is NF-κB signaling pathway-dependent. Lipopolysaccharide (LPS)-primed murine bone-marrow-derived macrophages were exposed to Co2+, Cr3+, or Ni2+, with or without an inhibitor of caspase-1, oxidative stress, or NF-κB. Culture supernatants were analyzed for active caspase-1 (immunoblotting) and/or IL-1β (ELISA). Overall, results showed that while both Cr3+ and Ni2+ may be inducing inflammasome activation, Cr3+ is likely a more potent activator, acting through oxidative stress and the NF-κB signaling pathway. Further elucidation of the activation mechanisms may facilitate the development of therapeutic approaches to modulate the inflammatory response to metal ions, and thereby increase implant longevity."]},{"key":"dc:format","label":"Dc Format","values":["application/pdf"]},{"key":"dc:title","label":"Title","values":["Molecular Mechanisms Involved in Interleukin-1β Release by Macrophages Exposed to Metal Ions from Implantable Biomaterials"]}]}],"canonical_facts":{"dc:contributor":["Catelas, Isabelle"],"dc:creator":["Ferko, Maxime-Alexandre"],"dc:date":["2018-03-23T18:27:32Z","2018"],"dc:description":["Metal ions released from implantable biomaterials have been associated with adverse biological reactions that can limit implant longevity. Previous studies have shown that, in macrophages, Co2+, Cr3+, and Ni2+ can activate the NLR family pyrin domain-containing protein 3 (NLPR3) inflammasome, which is responsible for interleukin(IL)-1β production through caspase-1. Furthermore, these ions are known to induce oxidative stress, and inflammasome priming is known to involve nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB) signaling. However, the mechanisms of inflammasome activation by metal ions remain largely unknown. The objectives of this thesis were to determine if, in macrophages: 1. IL-1β release induced by metal ions is caspase-1-dependent; 2. caspase-1 activation and IL-1β release induced by metal ions are oxidative stress-dependent; and 3. IL-1β release induced by metal ions is NF-κB signaling pathway-dependent. Lipopolysaccharide (LPS)-primed murine bone-marrow-derived macrophages were exposed to Co2+, Cr3+, or Ni2+, with or without an inhibitor of caspase-1, oxidative stress, or NF-κB. Culture supernatants were analyzed for active caspase-1 (immunoblotting) and/or IL-1β (ELISA). Overall, results showed that while both Cr3+ and Ni2+ may be inducing inflammasome activation, Cr3+ is likely a more potent activator, acting through oxidative stress and the NF-κB signaling pathway. Further elucidation of the activation mechanisms may facilitate the development of therapeutic approaches to modulate the inflammatory response to metal ions, and thereby increase implant longevity."],"dc:format":["application/pdf"],"dc:identifier":["http://hdl.handle.net/10393/37331","http://dx.doi.org/10.20381/ruor-21603"],"dc:language":["en"],"dc:publisher":["Université d'Ottawa / University of Ottawa"],"dc:subject":["bioengineering","biomedical engineering","biomaterials","biocompatibility","orthopaedics","implants","metal alloys","metal ions","adverse tissue reactions","immune response","inflammation","molecular mechanisms","inflammasome activation","NLRP3","NALP3","macrophages","bone marrow-derived macrophages"],"dc:title":["Molecular Mechanisms Involved in Interleukin-1β Release by Macrophages Exposed to Metal Ions from Implantable Biomaterials"],"dc:type":["Thesis"]},"updated_at":"2026-07-24T03:39:42Z"}