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dc.contributor.authorMukaro, Violet R
dc.contributor.authorQuach, Alex
dc.contributor.authorGahan, Michelle E
dc.contributor.authorBoog, Bernadette
dc.contributor.authorHuang, Zhi H
dc.contributor.authorGao, Xiuhui
dc.contributor.authorHaddad, Carol
dc.contributor.authorMahalingam, Suresh
dc.contributor.authorHii, Charles S
dc.contributor.authorFerrante, Antonio
dc.date.accessioned2019-07-05T12:31:53Z
dc.date.available2019-07-05T12:31:53Z
dc.date.issued2018
dc.identifier.issn2041-1723
dc.identifier.doi10.1038/s41467-018-03640-y
dc.identifier.urihttp://hdl.handle.net/10072/383580
dc.description.abstractDespite anti-TNF therapy advancements for inflammatory diseases such as rheumatoid arthritis, the burden of diseases remains high. An 11-mer TNF peptide, TNF70–80, is known to stimulate selective functional responses compared to the parent TNF molecule. Here, we show that TNF70–80 binds to the TNF receptor, activating p38 MAP kinase through TNF receptor-associated factor 2. Using truncated TNFR mutants, we identify the sequence in TNFRI which enables p38 activation by TNF70–80. Peptides with this TNFRI sequence, such as TNFRI206–211 bind to TNF and inhibit TNF-induced p38 activation, respiratory burst, cytokine production and adhesion receptor expression but not F-Met-Leu-Phe-induced respiratory burst in neutrophils. TNFRI206–211 does not prevent TNF binding to TNFRI or TNF-induced stimulation of ERK, JNK and NF-κB. TNFRI206–211 inhibits bacterial lipopolysaccharide-induced peritonitis, carrageenan-induced and antigen-induced paw inflammation, and respiratory syncytial virus-induced lung inflammation in mice. Our findings suggest a way of targeting TNF-p38 pathway to treat chronic inflammatory disorders.
dc.description.peerreviewedYes
dc.languageEnglish
dc.language.isoeng
dc.publisherNATURE PUBLISHING GROUP
dc.relation.ispartofjournalNATURE COMMUNICATIONS
dc.relation.ispartofvolume9
dc.subject.fieldofresearchMultidisciplinary
dc.subject.fieldofresearchcodeMD
dc.titleSmall tumor necrosis factor receptor biologics inhibit the tumor necrosis factor-p38 signalling axis and inflammation
dc.typeJournal article
dc.type.descriptionC1 - Articles
dc.type.codeC - Journal Articles
dcterms.licensehttp://creativecommons.org/licenses/by/4.0/
dc.description.versionVersion of Record (VoR)
gro.rights.copyrightThis article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/.
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gro.griffith.authorMahalingam, Suresh


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