{"id":{"repo_id":"iupui","oai_identifier":"oai:scholarworks.indianapolis.iu.edu:1805/6018"},"canonical_url":"https://search.dev.ndltd.org/etd/iupui/oai:scholarworks.indianapolis.iu.edu:1805/6018","repository":{"repo_id":"iupui","name":"IUPUI","base_url":"https://scholarworks.indianapolis.iu.edu/server/oai/request"},"display":{"title":"Vitamin D Inhibits Expression of Protein Arginine Deiminase 2 and 4 in Experimental Autoimmune Encephalomoyelitis Model Of Multiple Sclerosis","abstract":"Multiple sclerosis (MS) is a disabling disease that afflicts an estimated two million people worldwide. The disease is characterized by degradation of the myelin sheath that insulates neurons of the central nervous system manifesting as a heterogeneous collection of symptoms. Two enzymes, protein arginine deaminases type 2 and 4 (PAD2 and PAD4) have been implicated to play an etiologic role in demyelination and neurodegeneration by catalyzing a post-translational modification of arginine peptide residues to citrulline. The pathogenesis of MS is poorly understood, though vitamin D deficiency is a well-associated risk factor for developing the disorder. Using the experimental autoimmune encephalomyelitis (EAE) model of MS we demonstrate vitamin D treatment to attenuate over-expression of PAD 2 and 4 in the brain and spine during EAE. In addition, we identify two molecules produced by peripheral immune cells, IFNɣ and IL-6, as candidate signaling molecules that induce PAD expression in the brain. We demonstrate vitamin D treatment to inhibit IFNɣ mediated up regulation of PAD2 and PAD4 both directly within the brain and by modulating PAD-inducing cytokine production by infiltrating immune cells. These results provide neuroprotective rational for the supplementation of vitamin D in MS patients. More importantly, these results imply an epigenetic link between vitamin D deficiency and the pathogenesis of MS that merits further investigation.","abstract_html":"Multiple sclerosis (MS) is a disabling disease that afflicts an estimated two million people worldwide. The disease is characterized by degradation of the myelin sheath that insulates neurons of the central nervous system manifesting as a heterogeneous collection of symptoms. Two enzymes, protein arginine deaminases type 2 and 4 (PAD2 and PAD4) have been implicated to play an etiologic role in demyelination and neurodegeneration by catalyzing a post-translational modification of arginine peptide residues to citrulline. The pathogenesis of MS is poorly understood, though vitamin D deficiency is a well-associated risk factor for developing the disorder. Using the experimental autoimmune encephalomyelitis (EAE) model of MS we demonstrate vitamin D treatment to attenuate over-expression of PAD 2 and 4 in the brain and spine during EAE. In addition, we identify two molecules produced by peripheral immune cells, IFNɣ and IL-6, as candidate signaling molecules that induce PAD expression in the brain. We demonstrate vitamin D treatment to inhibit IFNɣ mediated up regulation of PAD2 and PAD4 both directly within the brain and by modulating PAD-inducing cytokine production by infiltrating immune cells. These results provide neuroprotective rational for the supplementation of vitamin D in MS patients. More importantly, these results imply an epigenetic link between vitamin D deficiency and the pathogenesis of MS that merits further investigation.","abstract_has_math":false,"creators":["McCain, Travis William"],"institution":null,"degree_name":null,"degree_level":null,"degree_discipline":null,"degree_department":null,"school":null,"contributors":[],"advisors":["Gallagher, Patricia J."],"committee_chairs":[],"committee_members":[],"year":2014,"date_issued":"2014","date_published":"2014","updated_at":"2026-07-24T02:42:13Z","subjects":["PAD2, PAD4, protein arginine deiminase, peptidyl arginine deiminase, vitamin D, 1,25(OH)2D3, multiple sclerosis, MS, EAE, experimental autoimmune encephalomyelitis, epigenetics, methylation, citrullination, citrulline"],"languages":["en_US"],"rights":["Attribution-NoDerivs 3.0 United States"],"rights_urls":["http://creativecommons.org/licenses/by-nd/3.0/us/"],"identifier_entries":[{"key":"dc:identifier.uri","label":"Identifier URI","values":["http://dx.doi.org/10.7912/C2/2013"],"render_values":[{"text":"http://dx.doi.org/10.7912/C2/2013","href":"http://dx.doi.org/10.7912/C2/2013","code":true}]}]},"links":{"outbound_url":"https://hdl.handle.net/1805/6018","outbound_label":"Handle","outbound_source":"dc:identifier.uri"},"metadata_groups":[{"id":"people","label":"People","entries":[{"key":"dc:contributor.advisor","label":"Advisor","values":["Gallagher, Patricia J."]},{"key":"dc:contributor.other","label":"Dc Contributor Other","values":["Tune, Johnathan D.","Bright, John J."]},{"key":"dc:creator","label":"Author","values":["McCain, Travis William"]}]},{"id":"academic_context","label":"Academic Context","entries":[{"key":"dc:date.accessioned","label":"Dc Date Accessioned","values":["2015-03-05T15:22:05Z"]},{"key":"dc:date.available","label":"Dc Date Available","values":["2015-08-02T09:30:41Z"]},{"key":"dc:date.issued","label":"Date","values":["2014"]},{"key":"dc:type","label":"Dc Type","values":["Thesis"]}]},{"id":"subjects_keywords","label":"Subjects and Keywords","entries":[{"key":"dc:subject","label":"Dc Subject","values":["PAD2, PAD4, protein arginine deiminase, peptidyl arginine deiminase, vitamin D, 1,25(OH)2D3, multiple sclerosis, MS, EAE, experimental autoimmune encephalomyelitis, epigenetics, methylation, citrullination, citrulline"]}]},{"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":["Attribution-NoDerivs 3.0 United States"]},{"key":"dc:rights.uri","label":"Rights URI","values":["http://creativecommons.org/licenses/by-nd/3.0/us/"]}]},{"id":"identifiers","label":"Identifiers","entries":[{"key":"dc:identifier.uri","label":"Identifier URI","values":["https://hdl.handle.net/1805/6018","http://dx.doi.org/10.7912/C2/2013"]}]},{"id":"additional","label":"Additional Metadata","entries":[{"key":"dc:description","label":"Description","values":["Indiana University-Purdue University Indianapolis (IUPUI)"]},{"key":"dc:description.abstract","label":"Abstract","values":["Multiple sclerosis (MS) is a disabling disease that afflicts an estimated two million people worldwide. The disease is characterized by degradation of the myelin sheath that insulates neurons of the central nervous system manifesting as a heterogeneous collection of symptoms. Two enzymes, protein arginine deaminases type 2 and 4 (PAD2 and PAD4) have been implicated to play an etiologic role in demyelination and neurodegeneration by catalyzing a post-translational modification of arginine peptide residues to citrulline. The pathogenesis of MS is poorly understood, though vitamin D deficiency is a well-associated risk factor for developing the disorder. Using the experimental autoimmune encephalomyelitis (EAE) model of MS we demonstrate vitamin D treatment to attenuate over-expression of PAD 2 and 4 in the brain and spine during EAE. In addition, we identify two molecules produced by peripheral immune cells, IFNɣ and IL-6, as candidate signaling molecules that induce PAD expression in the brain. We demonstrate vitamin D treatment to inhibit IFNɣ mediated up regulation of PAD2 and PAD4 both directly within the brain and by modulating PAD-inducing cytokine production by infiltrating immune cells. These results provide neuroprotective rational for the supplementation of vitamin D in MS patients. More importantly, these results imply an epigenetic link between vitamin D deficiency and the pathogenesis of MS that merits further investigation."]},{"key":"dc:title","label":"Title","values":["Vitamin D Inhibits Expression of Protein Arginine Deiminase 2 and 4 in Experimental Autoimmune Encephalomoyelitis Model Of Multiple Sclerosis"]}]}],"canonical_facts":{"dc:contributor.advisor":["Gallagher, Patricia J."],"dc:contributor.other":["Tune, Johnathan D.","Bright, John J."],"dc:creator":["McCain, Travis William"],"dc:date.accessioned":["2015-03-05T15:22:05Z"],"dc:date.available":["2015-08-02T09:30:41Z"],"dc:date.issued":["2014"],"dc:description":["Indiana University-Purdue University Indianapolis (IUPUI)"],"dc:description.abstract":["Multiple sclerosis (MS) is a disabling disease that afflicts an estimated two million people worldwide. The disease is characterized by degradation of the myelin sheath that insulates neurons of the central nervous system manifesting as a heterogeneous collection of symptoms. Two enzymes, protein arginine deaminases type 2 and 4 (PAD2 and PAD4) have been implicated to play an etiologic role in demyelination and neurodegeneration by catalyzing a post-translational modification of arginine peptide residues to citrulline. The pathogenesis of MS is poorly understood, though vitamin D deficiency is a well-associated risk factor for developing the disorder. Using the experimental autoimmune encephalomyelitis (EAE) model of MS we demonstrate vitamin D treatment to attenuate over-expression of PAD 2 and 4 in the brain and spine during EAE. In addition, we identify two molecules produced by peripheral immune cells, IFNɣ and IL-6, as candidate signaling molecules that induce PAD expression in the brain. We demonstrate vitamin D treatment to inhibit IFNɣ mediated up regulation of PAD2 and PAD4 both directly within the brain and by modulating PAD-inducing cytokine production by infiltrating immune cells. These results provide neuroprotective rational for the supplementation of vitamin D in MS patients. More importantly, these results imply an epigenetic link between vitamin D deficiency and the pathogenesis of MS that merits further investigation."],"dc:identifier.uri":["https://hdl.handle.net/1805/6018","http://dx.doi.org/10.7912/C2/2013"],"dc:language.iso":["en_US"],"dc:rights":["Attribution-NoDerivs 3.0 United States"],"dc:rights.uri":["http://creativecommons.org/licenses/by-nd/3.0/us/"],"dc:subject":["PAD2, PAD4, protein arginine deiminase, peptidyl arginine deiminase, vitamin D, 1,25(OH)2D3, multiple sclerosis, MS, EAE, experimental autoimmune encephalomyelitis, epigenetics, methylation, citrullination, citrulline"],"dc:title":["Vitamin D Inhibits Expression of Protein Arginine Deiminase 2 and 4 in Experimental Autoimmune Encephalomoyelitis Model Of Multiple Sclerosis"],"dc:type":["Thesis"]},"updated_at":"2026-07-24T02:42:13Z"}