C-Jun N-terminal kinase (JNK) inhibitor, SP600125, blocks interleukin (IL)–6-induced vascular endothelial growth factor (VEGF) production: cyclosporine A partially mimics this inhibitory effect

Naruishi, Koji; Nishimura, Fusanori; Yamada-Naruishi, Hisa; Omori, Kazuhiro; Yamaguchi, Mayumi; Takashiba, Shogo

doi:10.1097/01.tp.0000085661.52980.95

Cited by 33 publications

(33 citation statements)

References 10 publications

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“…VEGF is the most powerful regulator of angiogenesis, and plays an important role in the regulation of inflammatory periodontitis (6). Our previous reports have shown that IL-6/sIL-6R induced VEGF secretion in HGFs (18). As shown in Japan and Strategic Medical Science Research Centre from the Ministry of Education, Culture, Sports, Science, and Technology of Japan, 2010-2014.…”

Section: Growth Factors-possible Mechanisms Of Induction Of Angiogenesismentioning

confidence: 86%

“…Both IL-1β and IL-6/sIL-6R increased significantly IL-1ra and MCP-1 ylation of IL-6 signal transducer gp130 in HGFs (19). At least two distinct signaling cascades, the Stat3 and the MAPKs pathways, have been activated and lead to various responses such as VEGF secretion in HGFs (18). In the present study, we demonstrated for the first time that IL-1β but not IL-6/sIL-6R induces gp130 expression in HGFs at mRNA and protein levels.…”

Section: Discussionmentioning

confidence: 99%

“…In addition, it is well known that soluble form of IL-6R (sIL-6R) has agonistic functions of IL-6 and requires cells expressing the gp130 (27). This pathway allows cells that do not express surface IL-6R such as human gingival fibroblasts (HGFs) to respond to the presence of IL-6 (19), resulting in vascular endothelial growth factor (VEGF) production seen in periodontitis lesions (18). Exactly, we previously reported that IL-6 signals in the presence of sIL-6R are initiated in the phosphorylation of gp130 in human gingival fibroblasts (HGFs) (19).…”

Section: Methodsmentioning

confidence: 99%

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Enhancement of gingival inflammation induced by synergism of IL-1^|^beta; and IL-6

et al. 2013

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Internleukin-1 (IL-1) and IL-6 are the most potent proinflammatory cytokines being involved in inflammatory diseases such as periodontitis. The objective of this study was to examine the synergistic effects of IL-1β and IL-6 on gingival inflammation by targeting cultured human gingival fibroblasts (HGFs). HGFs were treated with IL-1β or IL-6/soluble IL-6R (sIL-6R), and total RNA and total cell lysate were collected to examine expression of gp130 known as a signal transducer of IL-6 using qRT-PCR and Western blotting. IL-1β-mediated IL-6 productivity in HGFs was examined using ELISA method. Likewise, after HGFs and THP-1 macrophages were treated with IL-1β, TNF-α and IL-6, sIL-6R productivity was examined. Next, HGFs were treated with IL-6/ sIL-6R after pretreatment of IL-1β, and the intracellular signals were examined using Western blotting. Finally, various mRNA/protein expressions in HGFs treated with IL-6/sIL-6R after pretreatment of IL-1β were examined using qRT-PCR and ELISA method. IL-1β increased significantly both gp130 and IL-6 expression in HGFs. IL-6 increased significantly sIL-6R production in THP-1 macrophages but not HGFs. Co-stimulation with IL-1β and IL-6/sIL-6R induced dramatically the phosphorylation of Stat3, ERK and JNK in HGFs. Interestingly, expression of various inflammation-related molecules such as MMP-1, MCP-1, IL-1ra, bFGF and VEGF were enhanced by co-stimulation with IL-1β and IL-6/sIL-6R in HGFs. Gingival inflammation is regulated by HGFs affected by both IL-1β and IL-6/sIL-6R synergistically through induction of gp130 expression, resulting in progression of periodontitis.

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Section: Growth Factors-possible Mechanisms Of Induction Of Angiogenesismentioning

confidence: 86%

Section: Discussionmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

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Enhancement of gingival inflammation induced by synergism of IL-1^|^beta; and IL-6

et al. 2013

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“…Thus, Cav-1 may co-relate to VEGF in inflamed lesions, leading to angiogenesis. Previously, we have reported that IL-6/sIL-6R promotes VEGF secretion in HGFs, and it is considered that HGFs possess the ability of VEGF production (20). Therefore, we examined whether secreted Cav-1 induces VEGF secretion in HGFs.…”

Section: Angiogenesismentioning

confidence: 96%

“…Fibroblasts such as HGFs are the most abundant cells in gingival connective tissues and play an important role in the control of inflammation (28,29). Recently, we demonstrated that VEGF expression is significantly induced by IL-6 in the presence of sIL-6R in HGFs (20 …”

Section: Cav-1 Induces Mrna Expression Of Various Inflammation-relatementioning

confidence: 99%

Secreted caveolin-1 enhances periodontal inflammation by targeting gingival fibroblasts

et al. 2013

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Caveolin-1 (Cav-1) is a membrane protein. Recently, it has been reported that secreted Cav-1 induces angiogenesis in inflammatory microenvironment. However, it is unclear that Cav-1 regulates gingival inflammation. Therefore, we investigated the Cav-1 function to periodontal cells. Expression of Cav-1 in human periodontitis tissues was examined pathologically. Secretion of Cav-1 from human gingival fibroblasts (HGFs) or human periodontal ligament cells (HPLFs) treated with IL-1β and TNF-α was examined using Western blotting. Likewise, intracellular signals induced by Cav-1 were examined. Finally, we examined whether the secreted Cav-1 induces production of inflammatory mediators in HGFs using ELISA or qRT-PCR. Pathologically, high expression of Cav-1 was observed in human periodontitis tissues. Cav-1 secretion increased in both cultured HGFs and HPLFs treated with IL-1β and TNF-α. Cav-1 induced phosphorylation of JNK and ERK, but not Stat3 in HGFs. Furthermore, Cav-1 increased proMMP-1 and VEGF secretion in HGFs, and the VEGF secretion was statistically suppressed by JNK inhibitor SP600125, but not ERK inhibitor PD98059. ProMMP-1 secretion was suppressed statistically by both SP600125 and PD98059. In addition, Cav-1 increased significantly MMP-1, -10 and

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Use of a fluorescent phosphoprotein dye to characterize oxidative stress-induced signaling pathway components in macrophage and epithelial cultures exposed to diesel exhaust particle chemicals

Wang

Xiao

et al. 2005

Electrophoresis

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A large body of evidence has shown that exposure to ambient particulate matter (PM) leads to asthma exacerbation through an excitation of allergic inflammation. Utilizing diesel exhaust particles (DEPs) as a model air pollutant, we and others have demonstrated that PM contains redox-active chemicals that generate inflammation through an oxidative stress mechanism. Recently, the strengths of proteomics have enabled us to demonstrate that organic DEP extracts induce a hierarchical expression pattern of oxidative stress-induced proteins in macrophages and epithelial cells. As a further extension of this work, we now employ a new phosphosensor fluorescent dye, Pro-Q Diamond, to elucidate the induction of phosphoproteins and intracellular signaling cascades that may play a role in DEP-induced inflammation. We demonstrate that DEPs induced the phosphorylation of several phosphoproteins that belong to a number of signaling pathways as well as other oxidative stress pathways. In combination with cytokine array, phosphoproteome analysis using Pro-Q Diamond allowed us to characterize the aromatic and polar chemicals of DEPs that are involved in the activation of three different mitogen-activated protein (MAP) kinase signaling pathways.

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C-Jun N-terminal kinase (JNK) inhibitor, SP600125, blocks interleukin (IL)–6-induced vascular endothelial growth factor (VEGF) production: cyclosporine A partially mimics this inhibitory effect

Cited by 33 publications

References 10 publications

Enhancement of gingival inflammation induced by synergism of IL-1^|^beta; and IL-6

Enhancement of gingival inflammation induced by synergism of IL-1^|^beta; and IL-6

Secreted caveolin-1 enhances periodontal inflammation by targeting gingival fibroblasts

Use of a fluorescent phosphoprotein dye to characterize oxidative stress-induced signaling pathway components in macrophage and epithelial cultures exposed to diesel exhaust particle chemicals

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