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dc.contributor.authorChen, Chun-Jen
dc.contributor.authorShi, Yan
dc.contributor.authorHearn, Arron
dc.contributor.authorFitzgerald, Katherine A.
dc.contributor.authorGolenbock, Douglas T.
dc.contributor.authorReed, George W.
dc.contributor.authorAkira, Shizuo
dc.contributor.authorRock, Kenneth L.
dc.date2022-08-11T08:10:05.000
dc.date.accessioned2022-08-23T16:55:12Z
dc.date.available2022-08-23T16:55:12Z
dc.date.issued2006-08-04
dc.date.submitted2008-10-31
dc.identifier.citationJ Clin Invest. 2006 Aug;116(8):2262-71. <a href="http://dx.doi.org/10.1172/JCI28075">Link to article on publisher's site</a>
dc.identifier.issn0021-9738 (Print)
dc.identifier.doi10.1172/JCI28075
dc.identifier.pmid16886064
dc.identifier.urihttp://hdl.handle.net/20.500.14038/42666
dc.description.abstractWhile it is known that monosodium urate (MSU) crystals cause the disease gout, the mechanism by which these crystals stimulate this inflammatory condition has not been clear. Here we find that the Toll/IL-1R (TIR) signal transduction adaptor myeloid differentiation primary response protein 88 (MyD88) is required for acute gouty inflammation. In contrast, other TIR adaptor molecules, TIRAP/Mal, TRIF, and TRAM, are not required for this process. The MyD88-dependent TLR1, -2, -4, -6, -7, -9, and -11 and IL-18 receptor (IL-18R) are not essential for MSU-induced inflammation. Moreover, MSU does not stimulate HEK cells expressing TLR1-11 to activate NF-kappaB. In contrast, mice deficient in the MyD88-dependent IL-1R showed reduced inflammatory responses, similar to those observed in MyD88-deficient mice. Similarly, mice treated with IL-1 neutralizing antibodies also showed reduced MSU-induced inflammation, demonstrating that IL-1 production and IL-1R activation play essential roles in MSU-triggered inflammation. IL-1R deficiency in bone marrow-derived cells did not affect the inflammatory response; however, it was required in non-bone marrow-derived cells. These results indicate that IL-1 is essential for the MSU-induced inflammatory response and that the requirement of MyD88 in this process is primarily through its function as an adaptor molecule in the IL-1R signaling pathway.
dc.language.isoen_US
dc.relation<a href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&list_uids=16886064&dopt=Abstract">Link to Article in PubMed</a>
dc.subjectAdaptor Proteins, Signal Transducing
dc.subjectAnimals
dc.subjectGout
dc.subjectInflammation
dc.subjectMice
dc.subjectMice, Inbred C57BL
dc.subjectMice, Knockout
dc.subjectMyeloid Differentiation Factor 88
dc.subjectReceptors, Interleukin-1
dc.subjectSignal Transduction
dc.subjectToll-Like Receptors
dc.subjectUric Acid
dc.subjectImmunology and Infectious Disease
dc.subjectLife Sciences
dc.subjectMedicine and Health Sciences
dc.titleMyD88-dependent IL-1 receptor signaling is essential for gouty inflammation stimulated by monosodium urate crystals
dc.typeJournal Article
dc.source.journaltitleThe Journal of clinical investigation
dc.source.volume116
dc.source.issue8
dc.identifier.legacyfulltexthttps://escholarship.umassmed.edu/cgi/viewcontent.cgi?article=1992&amp;context=oapubs&amp;unstamped=1
dc.identifier.legacycoverpagehttps://escholarship.umassmed.edu/oapubs/993
dc.identifier.contextkey659176
refterms.dateFOA2022-08-23T16:55:12Z
html.description.abstract<p>While it is known that monosodium urate (MSU) crystals cause the disease gout, the mechanism by which these crystals stimulate this inflammatory condition has not been clear. Here we find that the Toll/IL-1R (TIR) signal transduction adaptor myeloid differentiation primary response protein 88 (MyD88) is required for acute gouty inflammation. In contrast, other TIR adaptor molecules, TIRAP/Mal, TRIF, and TRAM, are not required for this process. The MyD88-dependent TLR1, -2, -4, -6, -7, -9, and -11 and IL-18 receptor (IL-18R) are not essential for MSU-induced inflammation. Moreover, MSU does not stimulate HEK cells expressing TLR1-11 to activate NF-kappaB. In contrast, mice deficient in the MyD88-dependent IL-1R showed reduced inflammatory responses, similar to those observed in MyD88-deficient mice. Similarly, mice treated with IL-1 neutralizing antibodies also showed reduced MSU-induced inflammation, demonstrating that IL-1 production and IL-1R activation play essential roles in MSU-triggered inflammation. IL-1R deficiency in bone marrow-derived cells did not affect the inflammatory response; however, it was required in non-bone marrow-derived cells. These results indicate that IL-1 is essential for the MSU-induced inflammatory response and that the requirement of MyD88 in this process is primarily through its function as an adaptor molecule in the IL-1R signaling pathway.</p>
dc.identifier.submissionpathoapubs/993
dc.contributor.departmentDepartment of Medicine, Division of Infectious Diseases and Immunology
dc.contributor.departmentDepartment of Medicine, Division of Preventive and Behavorial Medicine
dc.contributor.departmentDepartment of Pathology
dc.source.pages2262-71


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