Site specific mutations in the mature form of human IL-18 with enhanced biological activity and decreased neutralization by IL-18 binding protein

Cited 49 time in scopus
Metadata Downloads

Full metadata record

DC FieldValueLanguage
dc.contributor.authorSoo Hyun M Kim-
dc.contributor.authorT Azam-
dc.contributor.authorDo Young Yoon-
dc.contributor.authorL L Reznikov-
dc.contributor.authorDanlela Novick-
dc.contributor.authorMenachem Rubinstein-
dc.contributor.authorCharles Dinarello-
dc.date.accessioned2017-04-19T08:57:47Z-
dc.date.available2017-04-19T08:57:47Z-
dc.date.issued2001-
dc.identifier.issn0027-8424-
dc.identifier.uri10.1073/pnas.051634098ko
dc.identifier.urihttps://oak.kribb.re.kr/handle/201005/5386-
dc.description.abstractIL-18 can be considered a proinflammatory cytokine mediating disease as well as an immunostimulatory cytokine that is important for host defense against infection and cancer. The high-affinity, constitutively expressed, and circulating IL-18 binding protein (IL-18BP), which competes with cell surface receptors for IL-18 and neutralizes IL-18 activity, may act as a natural antiinflammatory as well as immunosuppressive molecule. In the present studies, the IL-18 precursor caspase-1 cleavage site was changed to a factor Xa site, and, after expression in Escherichia coli, mature IL-18 was generated by factor Xa cleavage. Mature IL-18 generated by factor Xa cleavage was fully active. Single point mutations in the mature IL-18 peptide were made, and the biological activities of the wild-type (WT) IL-18 were compared with those of the mutants. Mutants E42A and K89A exhibited 2-fold increased activity compared with WT IL-18. A double mutant, E42A plus K89A, exhibited 4-fold greater activity. Unexpectedly, IL-18BP failed to neutralize the double mutant E42A plus K89A compared with WT IL-18. The K89A mutant was intermediate in being neutralized by IL-18BP, whereas neutralization of the E42A mutant was comparable to that in the WT IL-18. The identification of E42 and K89 in the mature IL-18 peptide is consistent with previous modeling studies of IL-18 binding to IL-18BP and explains the unusually high affinity of IL-18BP for IL-18.-
dc.publisherNatl Acad Sciences-
dc.titleSite specific mutations in the mature form of human IL-18 with enhanced biological activity and decreased neutralization by IL-18 binding protein-
dc.title.alternativeSite specific mutations in the mature form of human IL-18 with enhanced biological activity and decreased neutralization by IL-18 binding protein-
dc.typeArticle-
dc.citation.titleProceedings of National Academy of Sciences of United States of America-
dc.citation.number6-
dc.citation.endPage3309-
dc.citation.startPage3304-
dc.citation.volume98-
dc.contributor.affiliatedAuthorDo Young Yoon-
dc.contributor.alternativeName김수현-
dc.contributor.alternativeNameAzam-
dc.contributor.alternativeName윤도영-
dc.contributor.alternativeNameReznikov-
dc.contributor.alternativeNameNovick-
dc.contributor.alternativeNameRubinstein-
dc.contributor.alternativeNameDinarello-
dc.identifier.bibliographicCitationProceedings of National Academy of Sciences of United States of America, vol. 98, no. 6, pp. 3304-3309-
dc.identifier.doi10.1073/pnas.051634098-
dc.description.journalClassY-
Appears in Collections:
1. Journal Articles > Journal Articles
Files in This Item:
  • There are no files associated with this item.


Items in OpenAccess@KRIBB are protected by copyright, with all rights reserved, unless otherwise indicated.