Blunted activation of NF-kappa B and NF-kappa B-dependent gene expression by geranylgeranylacetone: Involvement of unfolded protein response

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dc.contributor.authorHayakawa, K.
dc.contributor.authorHiramatsu, N.
dc.contributor.authorOkamura, M.
dc.contributor.authorYao, J.
dc.contributor.authorPaton, A.
dc.contributor.authorPaton, J.
dc.contributor.authorKitamura, M.
dc.date.issued2008
dc.descriptionCopyright © 2008 Elsevier Inc. All rights reserved.
dc.description.abstractGeranylgeranylacetone (GGA), an anti-ulcer agent, has anti-inflammatory potential against experimental colitis and ischemia-induced renal inflammation. However, molecular mechanisms involved in its anti-inflammatory effects are largely unknown. We found that, in glomerular mesangial cells, GGA blocked activation of nuclear factor-κB and consequent induction of monocyte chemoattractant protein 1 (MCP-1) by inflammatory cytokines. It was inversely correlated with induction of unfolded protein response (UPR) evidenced by expression of 78 kDa glucose-regulated protein (GRP78) and suppression of endoplasmic reticulum stress-responsive alkaline phosphatase. Various inducers of UPR including tunicamycin, thapsigargin, A23187, 2-deoxyglucose, dithiothreitol, and AB5 subtilase cytotoxin reproduced the suppressive effects of GGA. Furthermore, attenuation of UPR by stable transfection with GRP78 diminished the anti-inflammatory effects of GGA. These results disclosed a novel, UPR-dependent mechanism underlying the anti-inflammatory potential of GGA.
dc.description.statementofresponsibilityKunihiro Hayakawa, Nobuhiko Hiramatsu, Maro Okamura, Jian Yao, Adrienne W. Paton, James C. Paton and Masanori Kitamura
dc.identifier.citationBiochemical and Biophysical Research Communications, 2008; 365(1):47-53
dc.identifier.doi10.1016/j.bbrc.2007.10.115
dc.identifier.issn0006-291X
dc.identifier.issn1090-2104
dc.identifier.orcidPaton, J. [0000-0001-9807-5278]
dc.identifier.urihttp://hdl.handle.net/2440/50752
dc.language.isoen
dc.publisherAcademic Press Inc
dc.source.urihttps://doi.org/10.1016/j.bbrc.2007.10.115
dc.subjectGeranylgeranylacetone
dc.subjectMesangial cell
dc.subjectTumor necrosis factor-α
dc.subjectUnfolded protein response
dc.subjectEndoplasmic reticulum stress
dc.subjectMonocyte chemoattractant protein 1
dc.subjectNuclear factor-κB
dc.titleBlunted activation of NF-kappa B and NF-kappa B-dependent gene expression by geranylgeranylacetone: Involvement of unfolded protein response
dc.typeJournal article
pubs.publication-statusPublished

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