Cooperative interaction of nuclear factor-kappa B- and cis-regulatory enhancer binding protein-like factor binding elements in activating the interleukin-8 gene by pro-inflammatory cytokines.

Mukaida, Naofumi; Mahé, Yann F.; Matsushima, Kouji

doi:10.1016/s0021-9258(17)45336-1

Cited by 579 publications

(40 citation statements)

References 47 publications

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“…Our results indicated that IL-8 induction in PDL cells required the concomitant presence of 2 signals: one from IL-113, and the other directly from the mechanical stimulus. IL-8 expression is regulated primarily at the transcriptional level, and its promoter contains functional binding sites for NF-KB, C/EBP, and AP-l (Mukaida et al, 1990;Yasumoto et al, 1992). IL-I13 activates ERKs and p38 in various cell types (Fan et al, 2001;Suzuki et al, 2001), and induces IL-8 gene expression through AP-l and NF-KB in human vascular smooth-muscle cells (Jung et al, 2002).…”

Section: :K!vmentioning

confidence: 99%

Force-induced IL-8 from Periodontal Ligament Cells Requires IL-1β

et al. 2007

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During orthodontic tooth movement, mechanical stresses induce inflammatory reactions in the periodontal ligament (PDL). We hypothesized that chemokines released from PDL cells under mechanical stress regulate osteoclastogenesis, and investigated the profiles and mechanisms of chemokine expression by human PDL cells in response to mechanical stress. In vitro, shear stress and pressure force rapidly increased the gene and protein expressions of IL-8/CXCL8 by PDL cells. Consistently, amounts of IL-8 in the gingival crevicular fluid of healthy individuals increased within 2 to 4 days of orthodontic force application. The PDL cells constitutively expressed low levels of IL-1beta, which were not further increased by mechanical stress. Interestingly, neutralization of IL-1beta abolished IL-8 induction by mechanical stresses, indicating that IL-1beta is essential for IL-8 induction, presumably though autocrine or paracrine mechanisms. Finally, experiments with signal-specific inhibitors indicated that MAP kinase activation is essential for IL-8 induction.

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Section: :K!vmentioning

confidence: 99%

Force-induced IL-8 from Periodontal Ligament Cells Requires IL-1β

et al. 2007

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“…In this regard, several promoters that have closely spaced NF-KB and C/EBP binding sites have been cloned. Examples are the acute-phase response gene encoding serum amyloid Al as well as the angiotensinogen, IL-6, and IL-8 genes (12,20,26,29).…”

mentioning

confidence: 99%

Distinct Mechanisms for Regulation of the Interleukin-8 Gene Involve Synergism and Cooperativity between C/EBP and NF-κB

Stein

Baldwin

1993

Molecular and Cellular Biology

128

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The interleukin-8 promoter is transcriptionally activated by interleukin-1, tumor necrosis factor alpha, phorbol myristate acetate, or hepatitis B virus X protein through a sequence located between positions -91 and -71. This region contains an NF-kappa B-like and a C/EBP-like binding site. We show here that several members of the NF-kappa B family, including p65, p50, p52, and c-Rel, can bind to this region, confirming an authentic NF-kappa B binding site in the interleukin-8 promoter. Further, C/EBP binds only weakly to the interleukin-8 promoter site. Electrophoretic mobility shift assays with proteins overexpressed in COS cells and with nuclear extracts from tumor necrosis factor alpha-stimulated HeLa cells demonstrated a strong cooperative binding of C/EBP to its site when NF-kappa B is bound to its adjacent binding site. Transfection studies lead to a model that suggests a highly complex regulation of interleukin-8 gene expression at multiple levels: independent binding of C/EBP and NF-kappa B to their respective sites, cooperative binding of C/EBP and NF-kappa B to DNA, and positive synergistic activation through the C/EBP binding site and inhibition through the NF-kappa B binding site by combinations of C/EBP and NF-kappa B. Thus, the ultimate regulation of interleukin-8 gene expression depends on the ratio of cellular C/EBP and NF-kappa B.

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“…Both sites have been shown to be targets for IL-1 and tumor necrosis factor alpha stimulation (37); thus, it is likely that the induction of NF-KB by IL-1 and tumor necrosis factor alpha functions to stimulate gene expression from each site. Furthermore, the IL-8 promoter contains adjacent binding sites for C/EBP and NF-KB that cooperate in gene activation (58), and the angiotensinogen promoter contains overlapping binding sites for these two transcription factors (19). Preliminary data obtained with the IL-8 promoter show cooperative binding of NF-KB and C/EBP to their adjacent binding sites, resulting in a dose-dependent synergistic activation of the IL-8 promoter (78a).…”

Section: Discussionmentioning

confidence: 99%

“…These events induce C/EBP,B binding to the SRE and activate c-fos expression (55). Interestingly, several promoters of immune or acutephase response genes, such as the interleukin-6 (IL-6) gene, the IL-8 gene, and the angiotensinogen gene, have adjacent or overlapping binding sites for C/EBP and NF-KB (19, 40,58).…”

mentioning

confidence: 99%

Functional and Physical Associations between NF-κB and C/EBP Family Members: a Rel Domain-bZIP Interaction

Stein

Cogswell

Baldwin

1993

Molecular and Cellular Biology

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NF-kappa B and C/EBP represent distinct families of transcription factors that target unique DNA enhancer elements. The heterodimeric NF-kappa B complex is composed of two subunits, a 50- and a 65-kDa protein. All members of the NF-kappa B family, including the product of the proto-oncogene c-rel, are characterized by their highly homologous approximately 300-amino-acid N-terminal region. This Rel homology domain mediates DNA binding, dimerization, and nuclear targeting of these proteins. C/EBP contains the bZIP region, which is characterized by two motifs in the C-terminal half of the protein: a basic region involved in DNA binding and a leucine zipper motif involved in dimerization. The C/EBP family consist of several related proteins, C/EBP alpha, C/EBP beta, C/EBP gamma, and C/EBP delta, that form homodimers and that form heterodimers with each other. We now demonstrated the unexpected cross-coupling of members of the NF-kappa B family three members of the C/EBP family. NF-kappa B p65, p50, and Rel functionally synergize with C/EBP alpha, C/EBP beta, and C/EBP delta. This cross-coupling results in the inhibition of promoters with kappa B enhancer motifs and in the synergistic stimulation of promoters with C/EBP binding sites. These studies demonstrate that NF-kappa B augments gene expression mediated by a multimerized c-fos serum response element in the presence of C/EBP. We show a direct physical association of the bZIP region of C/EBP with the Rel homology domain of NF-kappa B. The cross-coupling of NF-kappa B with C/EBP highlights a mechanism of gene regulation involving an interaction between distinct transcription factor families.

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Cooperative interaction of nuclear factor-kappa B- and cis-regulatory enhancer binding protein-like factor binding elements in activating the interleukin-8 gene by pro-inflammatory cytokines.

Cited by 579 publications

References 47 publications

Force-induced IL-8 from Periodontal Ligament Cells Requires IL-1β

Force-induced IL-8 from Periodontal Ligament Cells Requires IL-1β

Distinct Mechanisms for Regulation of the Interleukin-8 Gene Involve Synergism and Cooperativity between C/EBP and NF-κB

Functional and Physical Associations between NF-κB and C/EBP Family Members: a Rel Domain-bZIP Interaction

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