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dc.contributor.authorBawadekar, Mandar
dc.contributor.authorGendron-Fitzpatrick, Annette
dc.contributor.authorRebernick, Ryan
dc.contributor.authorShim, Daeun
dc.contributor.authorWarner, Thomas F.
dc.contributor.authorNicholas, Anthony P.
dc.contributor.authorLundblad, Lennart K. A
dc.contributor.authorThompson, Paul R
dc.contributor.authorShelef, Miriam A.
dc.date2022-08-11T08:09:45.000
dc.date.accessioned2022-08-23T16:41:53Z
dc.date.available2022-08-23T16:41:53Z
dc.date.issued2016-07-22
dc.date.submitted2016-08-10
dc.identifier.citationArthritis Res Ther. 2016 Jul 22;18(1):173. doi: 10.1186/s13075-016-1068-0. <a href="http://dx.doi.org/10.1186/s13075-016-1068-0">Link to article on publisher's site</a>
dc.identifier.issn1478-6354 (Linking)
dc.identifier.doi10.1186/s13075-016-1068-0
dc.identifier.pmid27450561
dc.identifier.urihttp://hdl.handle.net/20.500.14038/39976
dc.description.abstractBACKGROUND: The relationship between lung and joint inflammation in rheumatoid arthritis is poorly understood. Lung inflammation with resultant protein citrullination may trigger anti-citrullinated protein antibodies, inflammation, and arthritis. Alternatively, lung and joint inflammation may be two manifestations of a single underlying pathology. The lung has increased citrullination and TNF-alpha levels are high in rheumatoid arthritis; however, it is unknown if TNF-alpha can induce lung protein citrullination. The citrullinating enzyme peptidylarginine deiminase 4 (PAD4) exacerbates TNF-alpha-induced arthritis, but a role for PAD4 in lung citrullination and TNF-alpha-induced lung inflammation has not been explored. Our aim was to use TNF-alpha-overexpressing mice to clarify the intersection of TNF-alpha, citrullination, PAD4, arthritis, and lung inflammation. METHODS: Lung protein citrullination in wild-type mice, mice that overexpress TNF-alpha systemically (TNF(+)), TNF(+)PAD4(+/+), and TNF(+)PAD4(-/-) mice was quantified by both gel electrophoresis using a citrulline probe and western blot. Hematoxylin and eosin (HandE)-stained lung sections from TNF(+)PAD4(+/+) and TNF(+)PAD4(-/-) mice were scored for lung inflammation. HandE-stained ankle joint sections from mice that overexpress TNF-alpha only in the lungs were assessed for arthritis. RESULTS: TNF(+) mice have increased lung protein citrullination. TNF(+)PAD4(-/-) mice do not have significantly reduced lung protein citrullination, but do have decreased lung inflammation compared to TNF(+)PAD4(+/+) mice. Mice that overexpress TNF-alpha only in the lungs do not develop arthritis. CONCLUSIONS: PAD4 exacerbates lung inflammation downstream of TNF-alpha without having a major role in generalized protein citrullination in inflamed lungs. Also, TNF-alpha-induced lung inflammation is not sufficient to drive murine arthritis.
dc.language.isoen_US
dc.relation<p><a href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&list_uids=27450561&dopt=Abstract">Link to Article in PubMed</a></p>
dc.rightsCopyright © The Author(s). 2016. Open Access.
dc.rights.urihttp://creativecommons.org/licenses/by/4.0/
dc.subjectCitrullination
dc.subjectExperimental arthritis
dc.subjectLung
dc.subjectPeptidylarginine deiminase 4
dc.subjectRheumatoid arthritis
dc.subjectTNF-α
dc.subjectBiochemistry
dc.subjectEnzymes and Coenzymes
dc.subjectMusculoskeletal Diseases
dc.subjectRheumatology
dc.titleTumor necrosis factor alpha, citrullination, and peptidylarginine deiminase 4 in lung and joint inflammation
dc.typeJournal Article
dc.source.journaltitleArthritis research and therapy
dc.source.volume18
dc.source.issue1
dc.identifier.legacyfulltexthttps://escholarship.umassmed.edu/cgi/viewcontent.cgi?article=3790&amp;context=oapubs&amp;unstamped=1
dc.identifier.legacycoverpagehttps://escholarship.umassmed.edu/oapubs/2785
dc.identifier.contextkey8956659
refterms.dateFOA2022-08-23T16:41:53Z
html.description.abstract<p>BACKGROUND: The relationship between lung and joint inflammation in rheumatoid arthritis is poorly understood. Lung inflammation with resultant protein citrullination may trigger anti-citrullinated protein antibodies, inflammation, and arthritis. Alternatively, lung and joint inflammation may be two manifestations of a single underlying pathology. The lung has increased citrullination and TNF-alpha levels are high in rheumatoid arthritis; however, it is unknown if TNF-alpha can induce lung protein citrullination. The citrullinating enzyme peptidylarginine deiminase 4 (PAD4) exacerbates TNF-alpha-induced arthritis, but a role for PAD4 in lung citrullination and TNF-alpha-induced lung inflammation has not been explored. Our aim was to use TNF-alpha-overexpressing mice to clarify the intersection of TNF-alpha, citrullination, PAD4, arthritis, and lung inflammation.</p> <p>METHODS: Lung protein citrullination in wild-type mice, mice that overexpress TNF-alpha systemically (TNF(+)), TNF(+)PAD4(+/+), and TNF(+)PAD4(-/-) mice was quantified by both gel electrophoresis using a citrulline probe and western blot. Hematoxylin and eosin (HandE)-stained lung sections from TNF(+)PAD4(+/+) and TNF(+)PAD4(-/-) mice were scored for lung inflammation. HandE-stained ankle joint sections from mice that overexpress TNF-alpha only in the lungs were assessed for arthritis.</p> <p>RESULTS: TNF(+) mice have increased lung protein citrullination. TNF(+)PAD4(-/-) mice do not have significantly reduced lung protein citrullination, but do have decreased lung inflammation compared to TNF(+)PAD4(+/+) mice. Mice that overexpress TNF-alpha only in the lungs do not develop arthritis.</p> <p>CONCLUSIONS: PAD4 exacerbates lung inflammation downstream of TNF-alpha without having a major role in generalized protein citrullination in inflamed lungs. Also, TNF-alpha-induced lung inflammation is not sufficient to drive murine arthritis.</p>
dc.identifier.submissionpathoapubs/2785
dc.contributor.departmentDepartment of Biochemistry and Molecular Pharmacology
dc.source.pages173


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Copyright © The Author(s). 2016. Open Access.
Except where otherwise noted, this item's license is described as Copyright © The Author(s). 2016. Open Access.