Two activator protein-1 elements in the matrix metalloproteinase-1 promoter have differential effects on transcription and bind Jun D, c-Fos, and Fra-2

White, Lori A.; Brinckerhoff, Constance E.

doi:10.1016/s0945-053x(05)80014-9

Cited by 81 publications

(83 citation statements)

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“…Binding to this site resulted in two specific complexes (Fig. 6), as reported in the literature (27,34). Further, specific binding to this AP-1 element was increased in extracts isolated from TCDD-treated NHK cultures.…”

Section: Fig 3 Atra Abolishes Tcdd-induced Binding To the Cyp1a1supporting

confidence: 80%

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Interaction between the Aryl Hydrocarbon Receptor and Retinoic Acid Pathways Increases Matrix Metalloproteinase-1 Expression in Keratinocytes

Murphy

Villano

Dorn

et al. 2004

Journal of Biological Chemistry

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Exposure to the environmental contaminant 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) results in a variety of pathological lesions in humans via activation of the aryl hydrocarbon receptor (AhR) pathway. It has become apparent that this pathway interacts with a variety of signaling pathways that are believed to be involved in mediating TCDD/AhR biological effects. Our hypothesis is that TCDD mediates these pathological lesions by directly altering the expression of genes involved in matrix deposition and remodeling and that the retinoic acid signaling pathway is involved in modulating TCDD-induced effects. Therefore, we examined the effect of TCDD and all-trans retinoic acid (atRA) on the expression of matrix metalloproteinase-1 (MMP-1, interstitial collagenase), one of the proteolytic enzymes that degrade type I collagen, in normal human keratinocytes. The data show that TCDD exposure results in increased MMP-1 expression in keratinocytes that is further enhanced by co-treatment with all-trans retinoic acid. TCDD-induced expression of MMP-1 appears to be mediated through two AP-1 elements in the proximal promoter of the MMP-1 gene. However, retinoic acid-mediated induction of keratinocyte MMP-1 is a result of both promoter activation and increased mRNA stability. These findings are the first to demonstrate TCDD-induced expression of MMP-1 and to demonstrate interactions between the TCDD/AhR and retinoic acid pathways on MMP-1 expression.Exposure to the polycyclic aromatic hydrocarbon 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) 1 results in a number of pathological lesions involving matrix deposition and tissue remodeling, including prostate and mammary tubule morphogenesis, palatal development, and tumor promotion (1-3). We hypothesize that TCDD mediates these pathological lesions by altering the expression of genes involved in matrix remodeling.Matrix metalloproteinases (MMPs) are a family of proteolytic enzymes that degrade the protein components of the extracellular matrix. MMP expression is integral to processes in skin remodeling and inappropriate expression and activity of MMPs is associated with a variety of pathologies such as rheumatoid arthritis and tumor metastasis (4 -6). Regulation of MMPs occurs primarily at the levels of transcription and activity (7). Investigation into MMP gene expression have identified several cis-and trans-acting factors that are involved in MMP-1 transcriptional activation, including several AP-1 sites and PEA-3 elements, that contribute to MMP-1 gene expression (8, 9).The primary mechanism of TCDD-induced changes in gene expression is through activation of the aryl hydrocarbon receptor (AhR)/aryl hydrocarbon receptor nuclear translocator (Arnt) transcription pathway. AhR and its dimerization partner, Arnt, are members of the basic helix-loop-helix PAS (bHLH-PAS) domain family of transcription factors. Proteins in this family have diverse biological roles ranging from regulation of development, hypoxia signaling, and circadian rhythms (reviewed in Ref.

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Section: Fig 3 Atra Abolishes Tcdd-induced Binding To the Cyp1a1supporting

confidence: 80%

“…Nuclear Extract Preparation and Electrophoretic Mobility Shift Assays (EMSA)-Nuclear extract harvest and mobility shift assays were performed as previously described (27). Nuclear proteins were isolated from Me 2 SO and TCDD treated adherent cultures of NHKs.…”

Section: Methodsmentioning

confidence: 99%

Interaction between the Aryl Hydrocarbon Receptor and Retinoic Acid Pathways Increases Matrix Metalloproteinase-1 Expression in Keratinocytes

Murphy

Villano

Dorn

et al. 2004

Journal of Biological Chemistry

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“…However, the paradoxical information that platelet-derived growth factor and fibroblast growth factor, which highly stimulate AP-1 activity, have no stimulatory effect on MMP1 strongly suggests that activation of AP-1 alone is not sufficient to stimulate MMP1 expression. Furthermore, results of an earlier study showed that mutation of the AP-1 element does not prevent phorbol induction of the MMP1 gene (15). These results indicate that involvement of other regulatory factors is necessary for proper induction of the MMP1 gene.…”

mentioning

confidence: 83%

“…The promoter region of the human MMP1 gene contains binding elements of several IL-1-responsive transcription factors, including 2 binding sites for activator protein 1 (AP-1) (14,15). In addition, a polyoma virus enhancer 3 (PEA-3) binding site at the proximal promoter region is also involved in the induction of human MMP1 (16).…”

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confidence: 99%

Induction of matrix metalloproteinase 1 gene expression is regulated by inflammation‐responsive transcription factor SAF‐1 in osteoarthritis

Ray¹,

Kuroki²,

Cook³

et al. 2003

Arthritis & Rheumatism

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Objective. To identify specific transcription factors that are activated in the cartilage tissue of osteoarthritis (OA) patients and are involved in the expression of matrix metalloproteinase 1 (MMP-1).Methods. DNase I footprint and electrophoretic mobility shift assays were performed to identify active elements of the MMP1 promoter and the transcription factors that interact with it. The relative abundance of the involved transcription factor in the cartilage was determined by immunohistochemical analysis. The role of serum amyloid A-activating factor 1 (SAF-1) in MMP-1 expression was assessed by transient transfection assay with plasmids containing either a functional or an antisense SAF-1 complementary DNA.Results. A novel promoter element was detected in the human MMP1 gene, and the inflammationresponsive transcription factor SAF-1 was found to interact with it. SAF-1 activity was detected in the chondrocytes of OA cartilage, where most of the cells stained positive for SAF-1. Overexpression of SAF-1 in OA chondrocytes increased the expression of the MMP1 promoter, and interference of endogenous SAF-1 activity by antisense SAF-1 messenger RNA inhibited interleukin-1-mediated MMP1 promoter activity.Conclusion. The results indicate that SAF-1 is involved in the regulation of MMP1 gene expression and it is highly abundant in the articular cartilage chondrocytes of OA patients. The data also demonstrate that control of SAF-1 activity can suppress induced expression of MMP-1. Conceivably, SAF-1 could be a potential therapeutic target to control the overexpression of MMP-1 associated with the pathogenesis of OA.

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“…AP-1 was examined because it is a key regulator of metalloproteinase (MP) gene expression and correlates with joint destruction (14). As shown in Figure 4, IT CHA significantly decreased AP-1 binding in nuclear extracts of arthritic joints.…”

Section: Effect Of It Cha On Synovial Ap-1 Bindingmentioning

confidence: 99%

Spinal adenosine receptor activation inhibits inflammation and joint destruction in rat adjuvant‐induced arthritis

Boyle

Moore

Yang

et al. 2002

Arthritis & Rheumatism

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Objective. To examine the effect of spinal cord adenosine (Ado) receptor stimulation on rat adjuvantinduced arthritis (AIA).Methods. Long-term intrathecal (IT) catheters were implanted into rats to provide spinal access for drug delivery. Animals were immunized with complete Freund's adjuvant at the tail base. Eight days later and every other day thereafter until day 20, rats were treated IT with the selective Ado A1 receptor agonist cyclohexyladenosine (CHA) or vehicle. In some experiments, animals received an additional daily intraperitoneal injection of the nonselective Ado antagonist theophylline. Paw swelling was measured by water displacement plethysmometry. The effect of IT CHA on the activation of activator protein 1 (AP-1) was determined by electromobility shift assay. Spinal cord c-Fos expression was determined by immunohistochemistry.Results. Spinal CHA significantly inhibited inflammation in AIA, with a mean ؎ SEM 20.9 ؎ 16.9% increase in paw swelling in the IT CHA group compared with 81.3 ؎ 10.6% in the saline group. The antiinflammatory effect of CHA was mediated through Ado receptors since the effect was reversed by coadministration of systemic theophylline. In addition, radiographs showed significantly less bone and cartilage destruction in the CHA-treated animals. Synovial expression of AP-1, which is a key regulator of metalloproteinase expression, was lower in IT CHA-treated animals. C-Fos expression was localized to spinal laminae I-VI, with a modest decrease observed in the superficial laminae in IT CHA-treated rats.Conclusion. These data demonstrate that the spinal cord can regulate peripheral inflammation. Therapeutic strategies that target the central nervous system might be useful in arthritis.The central nervous system (CNS) receives input from sites of peripheral inflammation and can, in turn, modulate the inflammatory process. For instance, inhibition of non-N-methyl-D-aspartate (NMDA) glutamate receptors in the lumbar dorsal horn suppresses knee swelling in rats after intraarticular injection with carrageenan. We have shown that spinal cord A1 adenosine (Ado) receptor agonists inhibit neutrophil accumulation in the skin of rats after intradermal injection with proinflammatory agents (1). In contrast to the knee edema model (2), this effect on neutrophil trafficking into peripheral sites is mediated by Ado-induced suppression of spinal NMDA receptor activation. The action of spinal cord Ado on neutrophil homing is independent of primary afferent fiber substance P and sympathetic neurons, but requires intact peripheral nerve connection since dorsal rhizotomy ablates the antiinflammatory activity (1).Understanding of the neural pathways and molecular mechanisms that process nociceptive information and subsequently regulate inflammatory peripheral responses is still in its formative stage. However, it is known that the spinal cord releases the excitatory amino acids glutamate and aspartate following nociceptive stimuli received via afferent C-fiber activation (3). Spinal cord neuronal re...

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Two activator protein-1 elements in the matrix metalloproteinase-1 promoter have differential effects on transcription and bind Jun D, c-Fos, and Fra-2

Cited by 81 publications

References 25 publications

Interaction between the Aryl Hydrocarbon Receptor and Retinoic Acid Pathways Increases Matrix Metalloproteinase-1 Expression in Keratinocytes

Interaction between the Aryl Hydrocarbon Receptor and Retinoic Acid Pathways Increases Matrix Metalloproteinase-1 Expression in Keratinocytes

Induction of matrix metalloproteinase 1 gene expression is regulated by inflammation‐responsive transcription factor SAF‐1 in osteoarthritis

Spinal adenosine receptor activation inhibits inflammation and joint destruction in rat adjuvant‐induced arthritis

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