Article: A dominant function of IKK/NF-κB signaling in global lipopolysaccharide-induced gene expression

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TitleA dominant function of IKK/NF-κB signaling in global lipopolysaccharide-induced gene expression
AuthorsCarayol, N3
Chen, J1
Yang, F3
Jin, T3
Jin, L2
States, D1
Wang, CY3
Issue Date2006
PublisherAmerican Society for Biochemistry and Molecular Biology, Inc. The Journal's web site is located at http://www.jbc.org/
CitationJournal Of Biological Chemistry, 2006, v. 281 n. 41, p. 31142-31151 [How to Cite?]
DOI: http://dx.doi.org/10.1074/jbc.M603417200
AbstractPorphyromonas gingivalis is an etiologic pathogen of periodontitis that is one of the most common inflammatory diseases. Recently, we found that P. gingivalis LPS activated the transcription factor nuclear factor-κB (NF-κB) through the IκB kinase complex (IKK). NF-κB is a transcription factor that controls inflammation and host responses. In this study, we examined the role of IKK/NF-κB in P. gingivalis LPS-induced gene expression on a genome-wide basis using a combination of microarray and biochemical approaches. A total of 88 early response genes were found to be induced by P. gingivalis LPS in a human THP.1 monocytic cell lines. Interestingly, the induction of most of these genes was abolished or attenuated under the inactivation of IKK/NF-κB. Among those IKK/NF-κB-dependent genes, 20 genes were NF-κB-inducible genes reported previously, and 59 genes represented putative novel NF-κB target genes. Using transcription factor binding analysis, we found that most of these putative NF-κB target genes contained one or multiple NF-κB-binding sites. Also, some transcription factor-binding motifs were overrepresented in the promoter of both known and putative NF-κB-dependent genes, indicating that these genes may be regulated in a similar fashion. Furthermore, we found that several transcription factors associated with metabolic and inflammatory responses, including nuclear receptors, activator of protein-1, and early growth responses, were induced by P. gingivalis LPS through IKK/NF-κB, indicating that IKK/NF-κB may utilize these transcription factors to mediate secondary responses. Taken together, our results demonstrate that IKK/NF-κB signaling plays a dominant role in P. gingivalis LPS-induced early response gene expression, suggesting that IKK/NF-κB is a therapeutic target for periodontitis. © 2006 by The American Society for Biochemistry and Molecular Biology, Inc.
ISSN0021-9258
2011 Impact Factor: 4.773
2011 SCImago Journal Rankings: 0.793
DOIhttp://dx.doi.org/10.1074/jbc.M603417200
ReferencesReferences in Scopus
DC Field
Value
dc.contributor.authorCarayol, N
dc.contributor.authorChen, J
dc.contributor.authorYang, F
dc.contributor.authorJin, T
dc.contributor.authorJin, L
dc.contributor.authorStates, D
dc.contributor.authorWang, CY
dc.date.accessioned2012-08-08T08:25:16Z
dc.date.available2012-08-08T08:25:16Z
dc.date.issued2006
dc.description.abstractPorphyromonas gingivalis is an etiologic pathogen of periodontitis that is one of the most common inflammatory diseases. Recently, we found that P. gingivalis LPS activated the transcription factor nuclear factor-κB (NF-κB) through the IκB kinase complex (IKK). NF-κB is a transcription factor that controls inflammation and host responses. In this study, we examined the role of IKK/NF-κB in P. gingivalis LPS-induced gene expression on a genome-wide basis using a combination of microarray and biochemical approaches. A total of 88 early response genes were found to be induced by P. gingivalis LPS in a human THP.1 monocytic cell lines. Interestingly, the induction of most of these genes was abolished or attenuated under the inactivation of IKK/NF-κB. Among those IKK/NF-κB-dependent genes, 20 genes were NF-κB-inducible genes reported previously, and 59 genes represented putative novel NF-κB target genes. Using transcription factor binding analysis, we found that most of these putative NF-κB target genes contained one or multiple NF-κB-binding sites. Also, some transcription factor-binding motifs were overrepresented in the promoter of both known and putative NF-κB-dependent genes, indicating that these genes may be regulated in a similar fashion. Furthermore, we found that several transcription factors associated with metabolic and inflammatory responses, including nuclear receptors, activator of protein-1, and early growth responses, were induced by P. gingivalis LPS through IKK/NF-κB, indicating that IKK/NF-κB may utilize these transcription factors to mediate secondary responses. Taken together, our results demonstrate that IKK/NF-κB signaling plays a dominant role in P. gingivalis LPS-induced early response gene expression, suggesting that IKK/NF-κB is a therapeutic target for periodontitis. © 2006 by The American Society for Biochemistry and Molecular Biology, Inc.
dc.description.natureLink_to_subscribed_fulltext
dc.identifier.citationJournal Of Biological Chemistry, 2006, v. 281 n. 41, p. 31142-31151 [How to Cite?]
DOI: http://dx.doi.org/10.1074/jbc.M603417200
dc.identifier.citeulike11369876
dc.identifier.doihttp://dx.doi.org/10.1074/jbc.M603417200
dc.identifier.epage31151
dc.identifier.isiWOS:000241075900089
dc.identifier.issn0021-9258
2011 Impact Factor: 4.773
2011 SCImago Journal Rankings: 0.793
dc.identifier.issue41
dc.identifier.pmid16914552
dc.identifier.scopuseid_2-s2.0-33750043186
dc.identifier.spage31142
dc.identifier.urihttp://hdl.handle.net/10722/154429
dc.identifier.volume281
dc.languageeng
dc.publisherAmerican Society for Biochemistry and Molecular Biology, Inc. The Journal's web site is located at http://www.jbc.org/
dc.publisher.placeUnited States
dc.relation.ispartofJournal of Biological Chemistry
dc.relation.referencesReferences in Scopus
dc.subject.meshAnimals
dc.subject.meshBase Sequence
dc.subject.meshGene Expression Regulation
dc.subject.meshGenes, Dominant
dc.subject.meshHumans
dc.subject.meshI-Kappa B Kinase - Metabolism
dc.subject.meshLipopolysaccharides - Metabolism
dc.subject.meshMice
dc.subject.meshMolecular Sequence Data
dc.subject.meshMonocytes - Microbiology
dc.subject.meshNf-Kappa B - Metabolism
dc.subject.meshPorphyromonas Gingivalis - Metabolism
dc.subject.meshSignal Transduction
dc.titleA dominant function of IKK/NF-κB signaling in global lipopolysaccharide-induced gene expression
dc.typeArticle
Author Affiliations
  1. University Michigan Ann Arbor
  2. The University of Hong Kong
  3. University of Michigan School of Dentistry