{"id":{"repo_id":"creighton","oai_identifier":"oai:cdr.creighton.edu:10504/87593"},"canonical_url":"https://search.dev.ndltd.org/etd/creighton/oai:cdr.creighton.edu:10504/87593","repository":{"repo_id":"creighton","name":"Creighton University","base_url":"https://cdr.creighton.edu/server/oai/request"},"display":{"title":"Effects of vitamin D on pro-inflammatory cytokines associated with Non-alcoholic fatty liver disease","abstract":"ABSTRACT|Non- alcoholic fatty liver disease (NAFLD) is the most common chronic liver disorder in the United States, affecting approximately one-third of the population. The prevalence of NAFLD increases to 90% in morbidly obese individuals. Many studies have shown a negative association between NAFLD and vitamin D levels. In fact, low vitamin D levels were correlated to histological severity, necro-inflammation and fibrosis in NAFLD. Vitamin D is recognized for its anti-inflammatory and anti-proliferative properties and mediates these functions through regulating and interrelating with inflammatory cytokines. We hypothesize that vitamin D may regulate gene expression by methods that would resolve ongoing inflammation in NAFLD by reducing the effects of pro-inflammatory cytokines, such as TNF-α, IL-1β, IL-6, IL-8, and up-regulate the effects of anti-inflammatory cytokine such as IL-10, produced in NAFLD and involve in its progression and severity. In our report these cytokines significantly increase mRNA and protein expression of importin-α3 and cyp24A1 and significantly decrease mRNA and protein expression of VDR, IκBα, and cyp27B1 in HepG-2. Treatment of HepG-2s with calcitriol significantly decrease mRNA and protein expression of importin-α3 and attenuate the effects of pro-inflammatory cytokines to induce importin-α3 mRNA and protein expression. IL-10, which is an anti- inflammatory cytokine, significantly reduced mRNA and protein expression of importin-α3 with or without calcitriol. Moreover, calcitriol up-regulates IкBα by increasing its mRNA and protein expression and attenuating the effects of proinflammatory cytokines to reduce mRNA and protein expression of IкBα in HepG-2s. IL-10 significantly increased mRNA and protein expression of IкBα as well as VDR in HepG-2. The effects of IL-10 on importin-α3, VDR and IкBα were further potentiated by calcitriol. Our data suggested that, under inflammatory conditions, calcitriol plays an inhibitory role in the regulation of NF-кB by decreasing the expression of importin α3 and increasing the expression of IкBα and VDR. Thus, calcitriol reduces the translocation of NF-кB and thereby downgrades its activity. Since NF-кB is the main transcription factor which plays a central role in inflammation and synthesis of pro-inflammatory cytokines; down-regulation of its activity offers an effective therapeutic method for alleviating chronic inflammation involved in the development of NAFLD.","abstract_html":"ABSTRACT|Non- alcoholic fatty liver disease (NAFLD) is the most common chronic liver disorder in the United States, affecting approximately one-third of the population. The prevalence of NAFLD increases to 90% in morbidly obese individuals. Many studies have shown a negative association between NAFLD and vitamin D levels. In fact, low vitamin D levels were correlated to histological severity, necro-inflammation and fibrosis in NAFLD. Vitamin D is recognized for its anti-inflammatory and anti-proliferative properties and mediates these functions through regulating and interrelating with inflammatory cytokines. We hypothesize that vitamin D may regulate gene expression by methods that would resolve ongoing inflammation in NAFLD by reducing the effects of pro-inflammatory cytokines, such as TNF-α, IL-1β, IL-6, IL-8, and up-regulate the effects of anti-inflammatory cytokine such as IL-10, produced in NAFLD and involve in its progression and severity. In our report these cytokines significantly increase mRNA and protein expression of importin-α3 and cyp24A1 and significantly decrease mRNA and protein expression of VDR, IκBα, and cyp27B1 in HepG-2. Treatment of HepG-2s with calcitriol significantly decrease mRNA and protein expression of importin-α3 and attenuate the effects of pro-inflammatory cytokines to induce importin-α3 mRNA and protein expression. IL-10, which is an anti- inflammatory cytokine, significantly reduced mRNA and protein expression of importin-α3 with or without calcitriol. Moreover, calcitriol up-regulates IкBα by increasing its mRNA and protein expression and attenuating the effects of proinflammatory cytokines to reduce mRNA and protein expression of IкBα in HepG-2s. IL-10 significantly increased mRNA and protein expression of IкBα as well as VDR in HepG-2. The effects of IL-10 on importin-α3, VDR and IкBα were further potentiated by calcitriol. Our data suggested that, under inflammatory conditions, calcitriol plays an inhibitory role in the regulation of NF-кB by decreasing the expression of importin α3 and increasing the expression of IкBα and VDR. Thus, calcitriol reduces the translocation of NF-кB and thereby downgrades its activity. Since NF-кB is the main transcription factor which plays a central role in inflammation and synthesis of pro-inflammatory cytokines; down-regulation of its activity offers an effective therapeutic method for alleviating chronic inflammation involved in the development of NAFLD.","abstract_has_math":false,"creators":["Ayouk, Nypiat Martin"],"institution":"Creighton University","degree_name":null,"degree_level":null,"degree_discipline":null,"degree_department":null,"school":null,"contributors":[],"advisors":["Agrawal, Devendra K."],"committee_chairs":[],"committee_members":[],"year":2016,"date_issued":"2016-05-10","date_published":"2016-05-10","updated_at":"2026-07-24T01:50:13Z","subjects":[],"languages":["en_US"],"rights":["Copyright is retained by the Author. A non-exclusive distribution right is granted to Creighton University and to ProQuest following the publishing model selected above."],"rights_urls":[],"identifier_entries":[]},"links":{"outbound_url":"http://hdl.handle.net/10504/87593","outbound_label":"Handle","outbound_source":"dc:identifier.uri"},"metadata_groups":[{"id":"people","label":"People","entries":[{"key":"dc:contributor.advisor","label":"Advisor","values":["Agrawal, Devendra K."]},{"key":"dc:creator","label":"Author","values":["Ayouk, Nypiat Martin"]}]},{"id":"academic_context","label":"Academic Context","entries":[{"key":"dc:date.accessioned","label":"Dc Date Accessioned","values":["2016-05-12T15:13:45Z"]},{"key":"dc:date.available","label":"Dc Date Available","values":["2018-05-12T13:40:18Z"]},{"key":"dc:date.issued","label":"Date","values":["2016-05-10"]},{"key":"dc:publisher","label":"Institution","values":["Creighton University"]},{"key":"dc:type","label":"Dc Type","values":["Thesis"]}]},{"id":"language_rights","label":"Language and Rights","entries":[{"key":"dc:language.iso","label":"Language (ISO)","values":["en_US"]},{"key":"dc:rights","label":"Dc Rights","values":["Copyright is retained by the Author. A non-exclusive distribution right is granted to Creighton University and to ProQuest following the publishing model selected above."]}]},{"id":"identifiers","label":"Identifiers","entries":[{"key":"dc:identifier.uri","label":"Identifier URI","values":["http://hdl.handle.net/10504/87593"]}]},{"id":"additional","label":"Additional Metadata","entries":[{"key":"dc:description.abstract","label":"Abstract","values":["ABSTRACT|Non- alcoholic fatty liver disease (NAFLD) is the most common chronic liver disorder in the United States, affecting approximately one-third of the population. The prevalence of NAFLD increases to 90% in morbidly obese individuals. Many studies have shown a negative association between NAFLD and vitamin D levels. In fact, low vitamin D levels were correlated to histological severity, necro-inflammation and fibrosis in NAFLD. Vitamin D is recognized for its anti-inflammatory and anti-proliferative properties and mediates these functions through regulating and interrelating with inflammatory cytokines. We hypothesize that vitamin D may regulate gene expression by methods that would resolve ongoing inflammation in NAFLD by reducing the effects of pro-inflammatory cytokines, such as TNF-α, IL-1β, IL-6, IL-8, and up-regulate the effects of anti-inflammatory cytokine such as IL-10, produced in NAFLD and involve in its progression and severity. In our report these cytokines significantly increase mRNA and protein expression of importin-α3 and cyp24A1 and significantly decrease mRNA and protein expression of VDR, IκBα, and cyp27B1 in HepG-2. Treatment of HepG-2s with calcitriol significantly decrease mRNA and protein expression of importin-α3 and attenuate the effects of pro-inflammatory cytokines to induce importin-α3 mRNA and protein expression. IL-10, which is an anti- inflammatory cytokine, significantly reduced mRNA and protein expression of importin-α3 with or without calcitriol. Moreover, calcitriol up-regulates IкBα by increasing its mRNA and protein expression and attenuating the effects of proinflammatory cytokines to reduce mRNA and protein expression of IкBα in HepG-2s. IL-10 significantly increased mRNA and protein expression of IкBα as well as VDR in HepG-2. The effects of IL-10 on importin-α3, VDR and IкBα were further potentiated by calcitriol. Our data suggested that, under inflammatory conditions, calcitriol plays an inhibitory role in the regulation of NF-кB by decreasing the expression of importin α3 and increasing the expression of IкBα and VDR. Thus, calcitriol reduces the translocation of NF-кB and thereby downgrades its activity. Since NF-кB is the main transcription factor which plays a central role in inflammation and synthesis of pro-inflammatory cytokines; down-regulation of its activity offers an effective therapeutic method for alleviating chronic inflammation involved in the development of NAFLD."]},{"key":"dc:title","label":"Title","values":["Effects of vitamin D on pro-inflammatory cytokines associated with Non-alcoholic fatty liver disease"]}]}],"canonical_facts":{"dc:contributor.advisor":["Agrawal, Devendra K."],"dc:creator":["Ayouk, Nypiat Martin"],"dc:date.accessioned":["2016-05-12T15:13:45Z"],"dc:date.available":["2018-05-12T13:40:18Z"],"dc:date.issued":["2016-05-10"],"dc:description.abstract":["ABSTRACT|Non- alcoholic fatty liver disease (NAFLD) is the most common chronic liver disorder in the United States, affecting approximately one-third of the population. The prevalence of NAFLD increases to 90% in morbidly obese individuals. Many studies have shown a negative association between NAFLD and vitamin D levels. In fact, low vitamin D levels were correlated to histological severity, necro-inflammation and fibrosis in NAFLD. Vitamin D is recognized for its anti-inflammatory and anti-proliferative properties and mediates these functions through regulating and interrelating with inflammatory cytokines. We hypothesize that vitamin D may regulate gene expression by methods that would resolve ongoing inflammation in NAFLD by reducing the effects of pro-inflammatory cytokines, such as TNF-α, IL-1β, IL-6, IL-8, and up-regulate the effects of anti-inflammatory cytokine such as IL-10, produced in NAFLD and involve in its progression and severity. In our report these cytokines significantly increase mRNA and protein expression of importin-α3 and cyp24A1 and significantly decrease mRNA and protein expression of VDR, IκBα, and cyp27B1 in HepG-2. Treatment of HepG-2s with calcitriol significantly decrease mRNA and protein expression of importin-α3 and attenuate the effects of pro-inflammatory cytokines to induce importin-α3 mRNA and protein expression. IL-10, which is an anti- inflammatory cytokine, significantly reduced mRNA and protein expression of importin-α3 with or without calcitriol. Moreover, calcitriol up-regulates IкBα by increasing its mRNA and protein expression and attenuating the effects of proinflammatory cytokines to reduce mRNA and protein expression of IкBα in HepG-2s. IL-10 significantly increased mRNA and protein expression of IкBα as well as VDR in HepG-2. The effects of IL-10 on importin-α3, VDR and IкBα were further potentiated by calcitriol. Our data suggested that, under inflammatory conditions, calcitriol plays an inhibitory role in the regulation of NF-кB by decreasing the expression of importin α3 and increasing the expression of IкBα and VDR. Thus, calcitriol reduces the translocation of NF-кB and thereby downgrades its activity. Since NF-кB is the main transcription factor which plays a central role in inflammation and synthesis of pro-inflammatory cytokines; down-regulation of its activity offers an effective therapeutic method for alleviating chronic inflammation involved in the development of NAFLD."],"dc:identifier.uri":["http://hdl.handle.net/10504/87593"],"dc:language.iso":["en_US"],"dc:publisher":["Creighton University"],"dc:rights":["Copyright is retained by the Author. A non-exclusive distribution right is granted to Creighton University and to ProQuest following the publishing model selected above."],"dc:title":["Effects of vitamin D on pro-inflammatory cytokines associated with Non-alcoholic fatty liver disease"],"dc:type":["Thesis"]},"updated_at":"2026-07-24T01:50:13Z"}