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dc.contributor.authorGray, Pearl
dc.contributor.authorMichelsen, Kathrin S.
dc.contributor.authorSirois, Cherilyn M.
dc.contributor.authorLowe, Emily
dc.contributor.authorShimada, Kenichi
dc.contributor.authorCrother, Timothy R.
dc.contributor.authorChen, Shuang
dc.contributor.authorBrikos, Constantinos
dc.contributor.authorBulut, Yonca
dc.contributor.authorLatz, Eicke
dc.contributor.authorUnderhill, David
dc.contributor.authorArditi, Moshe
dc.date2022-08-11T08:08:53.000
dc.date.accessioned2022-08-23T16:11:13Z
dc.date.available2022-08-23T16:11:13Z
dc.date.issued2010-06-01
dc.date.submitted2010-09-15
dc.identifier.citation<p>J Immunol. 2010 Jun 1;184(11):6359-66. Epub 2010 Apr 30.</p>
dc.identifier.issn1550-6606
dc.identifier.doi10.4049/jimmunol.0903543
dc.identifier.pmid20435923
dc.identifier.urihttp://hdl.handle.net/20.500.14038/33113
dc.description.abstractMyeloid differentiation factor 2 (MD-2) is a secreted gp that assembles with TLR4 to form a functional signaling receptor for bacterial LPS. In this study, we have identified a novel alternatively spliced isoform of human MD-2, termed MD-2 short (MD-2s), which lacks the region encoded by exon 2 of the MD-2 gene. Similar to MD-2, MD-2s is glycosylated and secreted. MD-2s also interacted with LPS and TLR4, but failed to mediate LPS-induced NF-kappaB activation and IL-8 production. We show that MD-2s is upregulated upon IFN-gamma, IL-6, and TLR4 stimulation and negatively regulates LPS-mediated TLR4 signaling. Furthermore, MD-2s competitively inhibited binding of MD-2 to TLR4. Our study pinpoints a mechanism that may be used to regulate TLR4 activation at the onset of signaling and identifies MD-2s as a potential therapeutic candidate to treat human diseases characterized by an overly exuberant or chronic immune response to LPS.
dc.language.isoen_US
dc.publisherAmerican Association of Immunologists
dc.relation<p><a href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=20435923&dopt=Abstract">Link to article in PubMed</a></p>
dc.relation.urlhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC3057206/
dc.subjectCell Line; Cell Separation; Enzyme-Linked Immunosorbent Assay; Flow Cytometry; Gene Expression; Gene Expression Profiling; Gene Expression Regulation; Humans; Immunoblotting; Immunoprecipitation; Interleukin-8; Lipopolysaccharides; Lymphocyte Antigen 96; Microscopy, Confocal; Protein Isoforms; Reverse Transcriptase Polymerase Chain Reaction; Signal Transduction; Toll-Like Receptor 4
dc.subjectImmunology and Infectious Disease
dc.subjectLife Sciences
dc.subjectMedicine and Health Sciences
dc.titleIdentification of a novel human MD-2 splice variant that negatively regulates Lipopolysaccharide-induced TLR4 signaling
dc.typeJournal Article
dc.source.journaltitleJournal of immunology (Baltimore, Md. : 1950)
dc.source.volume184
dc.source.issue11
dc.identifier.legacycoverpagehttps://escholarship.umassmed.edu/gsbs_sp/1656
dc.identifier.contextkey1558856
html.description.abstract<p>Myeloid differentiation factor 2 (MD-2) is a secreted gp that assembles with TLR4 to form a functional signaling receptor for bacterial LPS. In this study, we have identified a novel alternatively spliced isoform of human MD-2, termed MD-2 short (MD-2s), which lacks the region encoded by exon 2 of the MD-2 gene. Similar to MD-2, MD-2s is glycosylated and secreted. MD-2s also interacted with LPS and TLR4, but failed to mediate LPS-induced NF-kappaB activation and IL-8 production. We show that MD-2s is upregulated upon IFN-gamma, IL-6, and TLR4 stimulation and negatively regulates LPS-mediated TLR4 signaling. Furthermore, MD-2s competitively inhibited binding of MD-2 to TLR4. Our study pinpoints a mechanism that may be used to regulate TLR4 activation at the onset of signaling and identifies MD-2s as a potential therapeutic candidate to treat human diseases characterized by an overly exuberant or chronic immune response to LPS.</p>
dc.identifier.submissionpathgsbs_sp/1656
dc.contributor.departmentDepartment of Medicine, Division of Infectious Diseases and Immunology
dc.contributor.studentCherilyn M. Sirois


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