title: A dominant function of IKK/NF-kappaB signaling in global lipopolysaccharide-induced gene expression.
abstract: Porphyromonas 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-kappaB (NF-kappaB) through the IkappaB kinase complex (IKK). NF-kappaB is a transcription factor that controls inflammation and host responses. In this study, we examined the role of IKK/NF-kappaBin 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-kappaB. Among those IKK/NF-kappaB-dependent genes, 20 genes were NF-kappaB-inducible genes reported previously, and 59 genes represented putative novel NF-kappaB target genes. Using transcription factor binding analysis, we found that most of these putative NF-kappaB target genes contained one or multiple NF-kappaB-binding sites. Also, some transcription factor-binding motifs were overrepresented in the promoter of both known and putative NF-kappaB-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-kappaB, indicating that IKK/NF-kappaB may utilize these transcription factors to mediate secondary responses. Taken together, our results demonstrate that IKK/NF-kappaB signaling plays a dominant role in P. gingivalis LPS-induced early response gene expression, suggesting that IKK/NF-kappaB is a therapeutic target for periodontitis.
authors.affiliation: Laboratory of Molecular Signaling and Apoptosis, Department of Biologic and Materials Sciences, University of Michigan, Ann Arbor, Michigan 48109, USA.
authors.forename: Nathalie
authors.initials: N
authors.lastname: Carayol
authors.forename: Ji
authors.initials: J
authors.lastname: Chen
authors.forename: Fan
authors.initials: F
authors.lastname: Yang
authors.forename: Taocong
authors.initials: T
authors.lastname: Jin
authors.forename: Lijian
authors.initials: L
authors.lastname: Jin
authors.forename: David
authors.initials: D
authors.lastname: States
authors.forename: Cun-Yu
authors.initials: CY
authors.lastname: Wang
mesh_terms: D000818:Animals; D001483:Base Sequence; D005786:Gene Expression Regulation; D005799:Genes, Dominant; D006801:Humans; D051550:I-kappa B Kinase / Q000378:metabolism*; D008070:Lipopolysaccharides / Q000378:metabolism*; D051379:Mice; D008969:Molecular Sequence Data; D009000:Monocytes / Q000382:microbiology; D016328:NF-kappa B / Q000378:metabolism*; D016966:Porphyromonas gingivalis / Q000378:metabolism; D015398:Signal Transduction
chemical_list: D008070:Lipopolysaccharides; D016328:NF-kappa B; D051550:I-kappa B Kinase