Tumor necrosis factor-α stimulates human amelotin gene transcription in gingival epithelial cells

Yamazaki, Mizuho; Iwai, Yasunobu; Nöda, Keisuke; Matsui, Sari; Kato, Ayako; Takai, Hideki; Nakayama, Yohei; Ogata, Yorimasa

doi:10.1007/s00011-017-1126-3

Cited by 8 publications

(24 citation statements)

References 28 publications

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“…We have shown that AMTN gene expression is temporarily increased at the initiation of apoptosis by TGF‐β1 . TNF‐α stimulates human AMTN gene transcription in gingival epithelial cells . AMTN protein expression in the JE was increased in Porphyromonas gingivalis ‐infected periodontitis model mice at early stage, whereas AMTN protein levels were suppressed at later stages .…”

Section: Discussionmentioning

confidence: 95%

“…The promoter sequence between −353 and +1 of the human AMTN gene contains an inverted TATA box (nts −21 to −12), an inverted CCAAT box (nts −67 to −63), an activator protein 1 (AP1; nts −94 to −84), a CCAAT/enhancer binding protein 1 (C/EBP1; nts −118 to −105), an octamer transcription factor 1 element (Oct1; nts −129 to −117), a C/EBP2 (nts −163 to −150), a Ying Yang 1 (YY1; nts −228 to −212), and a specificity protein 1 (SP1; −351 to −328; Fig. ) . To determine the IL‐1β response regions in the human AMTN gene promoter, luciferase (LUC) constructs including various lengths of human AMTN gene promoter were transiently transfected into Ca9‐22 cells and their transcriptional activities were analyzed in the presence or absence of IL‐1β.…”

Section: Resultsmentioning

confidence: 99%

“…Inflammatory cytokines such as IL‐1β, tumor necrosis factor‐α (TNF‐α), and IL‐6 are soluble proteins that bind to specific receptors and induce intracellular signaling cascades . They play a fundamental role in inflammation including periodontal disease . Having pivotal and wide‐ranging function in innate immunity and inflammation, IL‐1β regulates adaptive immunity and stimulates connective tissue turnover .…”

Section: Discussionmentioning

confidence: 99%

“…We have previously reported that AMTN gene expression was increased in inflamed gingiva in patients with chronic periodontitis . Therefore, the regulation of AMTN gene transcription by IL‐1β in gingival epithelial cells is a crucial topic for onset and progression of periodontitis.…”

mentioning

confidence: 99%

“…In this study, we used human gingival epithelial Ca9‐22 cells. They have similar characteristics to those of JE‐derived cells, because they express AMTN and FDC‐SP, which are components of the internal basal lamina of JE .…”

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confidence: 99%

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Transcriptional regulation of human amelotin gene by interleukin‐1β

et al. 2018

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One of the major causes of tooth loss is chronic inflammation of the periodontium, the tissues surrounding the tooth. Amelotin ( AMTN ) is a tooth enamel protein which is expressed in maturation‐stage ameloblasts and also in the internal basal lamina of junctional epithelium, a unique epithelial structure attached to the tooth surface which protects against the constant microbiological challenge to the periodontium. Localization of AMTN suggests that its function could be involved in the dentogingival attachment. The purpose of this study was to investigate the effect of interleukin‐1β ( IL ‐1β) on AMTN gene transcription in human gingival epithelial Ca9‐22 cells. IL ‐1β increased AMTN mRNA and protein levels at 3 h, and the levels reached maximum at 6 and 12 h. IL ‐1β induced luciferase activities of human AMTN gene promoter constructs (−211, −353, −501, −769, and −950AMTN), but these activities were partially inhibited in −353AMTN constructs that included 3‐bp mutations in CCAAT /enhancer binding protein 1 (C/ EBP 1), C/ EBP 2, and Ying Yang 1 ( YY 1) elements. Transcriptional activities induced by IL ‐1β were abrogated by protein kinase A ( PKA ), tyrosine kinase, mitogen‐activated protein kinase kinase ( MEK 1/2), and phosphatidylinositol 3‐kinase ( PI 3K) inhibitors. Gel shift and ChIP assays showed that IL ‐1β increased C/ EBP β binding to C/ EBP 1 and C/ EBP 2, and YY 1 binding to YY 1 elements after 3 h, and that these DNA –protein interactions were inhibited by PKA , tyrosine kinase, MEK 1/2, and PI 3K inhibitors. These results demonstrated that IL ‐1β increases AMTN gene transcription in human gingival epithelial cells mediated through C/ EBP 1, C/ EBP 2, and YY 1 elements in the human AMTN gene promoter.

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Section: Discussionmentioning

confidence: 95%

Section: Resultsmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

mentioning

confidence: 99%

mentioning

confidence: 99%

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Transcriptional regulation of human amelotin gene by interleukin‐1β

et al. 2018

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C/EBPβ and YY1 bind and interact with Smad3 to modulate lipopolysaccharide‐induced amelotin gene transcription in mouse gingival epithelial cells

et al. 2018

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Junctional epithelium (JE) develops from reduced enamel epithelium during tooth formation and is critical for the maintenance of healthy periodontal tissue through ensuring appropriate immune responses and the rapid turnover of gingival epithelial cells. We have previously shown a relationship between inflammatory cytokines and expression of JE‐specific genes, such as amelotin (AMTN), in gingival epithelial cells. Here, we elucidated the effects of Porphyromonas gingivalis‐derived lipopolysaccharide (PgLPS) on Amtn gene transcription and the interaction of transcription factors. To determine the molecular basis of transcriptional regulation of the Amtn gene by PgLPS, we performed real‐time PCR and carried out luciferase assays using a mouse Amtn gene promoter linked to a luciferase reporter gene in mouse gingival epithelial GE1 cells. Gel mobility shift and chromatin immunoprecipitation assays were performed to identify response elements bound to LPS‐induced transcription factors. Next, we analyzed protein levels of the LPS‐induced transcription factors and the interaction of transcription factors by western blotting and immunoprecipitation. LPS increased Amtn mRNA levels and elevated luciferase activities of constructs containing regions between −116 and −238 of the mouse Amtn gene promoter. CCAAT/enhancer‐binding protein (C/EBP) 1–, C/EBP2– and Ying Yang 1 (YY1)–nuclear protein complexes were increased by LPS treatment. Furthermore, we identified LPS‐modulated interactions with C/EBPβ, YY1 and Smad3. These results demonstrate that PgLPS regulates Amtn gene transcription via binding of C/EBPβ–Smad3 and YY1–Smad3 complexes to C/EBP1, C/EBP2 and YY1 response elements in the mouse Amtn gene promoter.

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Negative feedback by SNAI2 regulates TGFβ1‐induced amelotin gene transcription in epithelial–mesenchymal transition

Nakayama

Tsuruya

Nöda

et al. 2018

Journal Cellular Physiology

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Junctional epithelium (JE) demonstrates biological responses with the rapid turnover of gingival epithelial cells. The state occurs in inflammation of gingiva and wound healing after periodontal therapy. To understand the underlying mechanisms and to maintain homeostasis of JE, it is important to investigate roles of JE‐specific genes. Amelotin (AMTN) is localized at JE and regulated by inflammatory cytokines and apoptotic factors that represent a critical role of AMTN in stabilizing the dentogingival attachment, which is an entrance of oral bacteria. In this study, we demonstrated that the AMTN gene expression was regulated by SNAI2 and transforming growth factor β1 (TGFβ1)‐induced epithelial–mesenchymal transition (EMT) that occurs in wound healing and fibrosis during chronic inflammation. SNAI2 downregulated AMTN gene expression via SNAI2 bindings to E‐boxes (E2 and E4) in the mouse AMTN gene promoter in EMT of gingival epithelial cells. Meanwhile, TGFβ1‐induced AMTN gene expression was attenuated by SNAI2 and TGFβ1‐induced SNAI2, without inhibition of the TGFβ1‐Smad3 signaling pathway. Moreover, SNAI2 small interfering RNA (siRNA) rescued SNAI2‐induced downregulation of AMTN gene expression, and TGFβ1‐induced AMTN gene expression was potentiated by SNAI2 siRNA. Taken together, these data demonstrated that AMTN gene expression in the promotion of EMT was downregulated by SNAI2. The inhibitory effect of AMTN gene expression was an independent feedback on the TGFβ1‐Smad3 signaling pathway, suggesting that the mechanism can be engaged in maintaining homeostasis of gingival epithelial cells at JE and the wound healing phase.

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Tumor necrosis factor-α stimulates human amelotin gene transcription in gingival epithelial cells

Abstract: These findings demonstrated that TNF-α stimulates AMTN gene transcription in human gingival epithelial cells via C/EBP1, C/EBP2, and YY1 elements in the human AMTN gene promoter.

Cited by 8 publications

References 28 publications

Transcriptional regulation of human amelotin gene by interleukin‐1β

Transcriptional regulation of human amelotin gene by interleukin‐1β

C/EBPβ and YY1 bind and interact with Smad3 to modulate lipopolysaccharide‐induced amelotin gene transcription in mouse gingival epithelial cells

Negative feedback by SNAI2 regulates TGFβ1‐induced amelotin gene transcription in epithelial–mesenchymal transition

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