Anti-inflammatory subtilase cytotoxin up-regulates A20 through the unfolded protein response

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dc.contributor.authorNakajima, S.
dc.contributor.authorSaito, Y.
dc.contributor.authorTakahashi, S.
dc.contributor.authorHiramatsu, N.
dc.contributor.authorKato, H.
dc.contributor.authorJohno, H.
dc.contributor.authorYao, J.
dc.contributor.authorPaton, A.
dc.contributor.authorPaton, J.
dc.contributor.authorKitamura, M.
dc.date.issued2010
dc.description.abstractWe recently reported that subtilase cytotoxin (SubAB) has the potential to attenuate experimental models of inflammatory diseases [3]. Currently, little is known about underlying mechanisms involved in this therapeutic effect. In the present report, we show that SubAB induces A20, the endogenous negative regulator of NF-kappaB, in vitro and in vivo. This stimulatory effect occurred at the transcriptional level, and SubAB induced activation of the A20 promoter. We found that, in the early phase, SubAB triggered activation of NF-kappaB in a dose-dependent manner. Blockade of NF-kappaB abrogated expression of A20 by SubAB. SubAB rapidly triggered the unfolded protein response (UPR), and induction of the UPR by other agents (thapsigargin and A23187) mimicked the stimulatory effects of SubAB, both on NF-kappaB and on A20. The induction of A20 by thapsigargin was correlated with activation of the A20 promoter, which was not observed in the kappaB-mutated A20 promoter. Furthermore, induction of A20 by SubAB was substantially attenuated by treatment with different chemical chaperones. These results elucidated for the first time that the anti-inflammatory SubAB has the potential to induce A20 through the UPR-NF-kappaB-dependent pathway.
dc.description.statementofresponsibilityShotaro Nakajima, Yukinori Saito, Shuhei Takahashi, Nobuhiko Hiramatsu, Hironori Kato, Hisashi Johno, Jian Yao, Adrienne W. Paton, James C. Paton, Masanori Kitamura
dc.identifier.citationBiochemical and Biophysical Research Communications, 2010; 397(2):176-180
dc.identifier.doi10.1016/j.bbrc.2010.05.069
dc.identifier.issn0006-291X
dc.identifier.issn1090-2104
dc.identifier.orcidPaton, J. [0000-0001-9807-5278]
dc.identifier.urihttp://hdl.handle.net/2440/60796
dc.language.isoen
dc.publisherAcademic Press Inc
dc.rightsCopyright © 2010 Elsevier Inc. All rights reserved.
dc.source.urihttps://doi.org/10.1016/j.bbrc.2010.05.069
dc.subjectSubtilase cytotoxin
dc.subjectA20
dc.subjectUnfolded protein response
dc.subjectNF-κB
dc.titleAnti-inflammatory subtilase cytotoxin up-regulates A20 through the unfolded protein response
dc.typeJournal article
pubs.publication-statusPublished

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