A JNK1/AP-1–Dependent, COX-2 Induction Is Implicated in 12-O-Tetradecanoylphorbol-13-Acetate–Induced Cell Transformation through Regulating Cell Cycle Progression

Zhang, Dongyun; Li, Jingxia; Song, Lun; Ouyang, Wei; Gao, Jimin; Huang, Chuanshu

doi:10.1158/1541-7786.mcr-07-0181

Cited by 20 publications

(15 citation statements)

References 55 publications

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“…In addition, we have also shown that GHRP-2 may potentially target to p38, JNK, and NF-κB in order to down-regulate PDD-induced phosphorylation of p38 and JNK (Figure 7A,B), AP-1 reporter activation (Figure 7D) and PDD-activated NF-κB nuclear translocation and reporter activation (Figure 8). In fact, the involvement of the AP-1 and NF-κB responsive elements in the regulation of the COX-2 [53,55] and IL-8 [56,57] promoters has been reported previously, which supports our findings that AP-1 and NF-κB are two important signaling targets involved in the anti-inflammatory function of GHRP-2 during the PKC-induced transcription of COX-2 and IL-8. Interestingly, ERK phosphorylation was induced by GHRP-2 (Figure 7C).…”

Section: Discussionsupporting

confidence: 93%

Growth Hormone Releasing Peptide-2 Attenuation of Protein Kinase C-Induced Inflammation in Human Ovarian Granulosa Cells

Chao

Sun

Peng

et al. 2016

IJMS

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Cyclooxygenase-2 (COX-2) and interleukin-8 (IL-8) are two important inflammatory mediators in ovulation. Ghrelin may modulate inflammatory signaling via growth hormone secretagogue receptors. We investigated the role of ghrelin in KGN human ovarian granulosa cells using protein kinase C (PKC) activator phorbol 12, 13-didecanoate (PDD) and synthetic ghrelin analog growth hormone releasing peptide-2 (GHRP-2). GHRP-2 attenuated PDD-induced expression of protein and mRNA, the promoter activity of COX-2 and IL-8 genes, and the secretion of prostaglandin E2 (PGE2) and IL-8. GHRP-2 promoted the degradation of PDD-induced COX-2 and IL-8 proteins with the involvement of proteasomal and lysosomal pathways. PDD-mediated COX-2 production acts via the p38, c-Jun N-terminal kinase (JNK), extracellular signal-regulated kinase (ERK) and nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB) pathways; PDD-mediated IL-8 production acts via the p38, JNK and ERK pathways. GHRP-2 reduced the PDD-induced phosphorylation of p38 and JNK and activator protein 1 (AP-1) reporter activation and PDD-induced NF-κB nuclear translocation and reporter activation. The inhibitors of mitogen-activated protein kinase phosphatase-1 (MKP-1) and protein phosphatase 2 (PP2A) reduced the inhibitory effect of GHRP-2 on PDD-induced COX-2 and IL-8 expression. Our findings demonstrate an anti-inflammatory role for ghrelin (GHRP-2) in PKC-mediated inflammation of granulosa cells, at least in part, due to its inhibitory effect on PKC-induced activation of p38, JNK and NF-κB, possibly by targeting to MKP-1 and PP2A.

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Section: Discussionsupporting

confidence: 93%

Growth Hormone Releasing Peptide-2 Attenuation of Protein Kinase C-Induced Inflammation in Human Ovarian Granulosa Cells

Chao

Sun

Peng

et al. 2016

IJMS

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“…The c-Jun/AP-1 pathway is crucial for COX-2 induction caused by some environmental stresses (Ouyang et al 2007a; Zhang et al 2008). Because of the multiple functions of AP-1 proteins, the selection of the different AP-1 dimers is considered as another mechanism for the modulation of AP-1 activity (Song et al 2008).…”

Section: Discussionmentioning

confidence: 99%

Hexavalent Chromium Cr(VI) Up-Regulates COX-2 Expression through an NFκB/c-Jun/AP-1–Dependent Pathway

Zuo

Cai

et al. 2012

Environ Health Perspect

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Background: Hexavalent chromium [Cr(VI)] is recognized as a human carcinogen via inhalation. However, the molecular mechanisms by which Cr(VI) causes cancers are not well understood.Objectives: We evaluated cyclooxygenase-2 (COX-2) expression and the signaling pathway leading to this induction due to Cr(VI) exposure in cultured cells.Methods: We used the luciferase reporter assay and Western blotting to determine COX-2 induction by Cr(VI). We used dominant negative mutant, genetic knockout, gene knockdown, and chromatin immunoprecipitation approaches to elucidate the signaling pathway leading to COX-2 induction.Results: We found that Cr(VI) exposure induced COX-2 expression in both normal human bronchial epithelial cells and mouse embryonic fibroblasts in a concentration- and time-dependent manner. Deletion of IKKβ [inhibitor of transcription factor NFκB (IκB) kinase β; an upstream kinase responsible for nuclear factor κB (NFκB) activation] or overexpression of TAM67 (a dominant-negative mutant of c-Jun) dramatically inhibited the COX-2 induction due to Cr(VI), suggesting that both NFκB and c-Jun/AP-1 pathways were required for Cr(VI)-induced COX-2 expression. Our results show that p65 and c-Jun are two major components involved in NFκB and AP-1 activation, respectively. Moreover, our studies suggest crosstalk between NFκB and c-Jun/AP-1 pathways in cellular response to Cr(VI) exposure for COX-2 induction.Conclusion: We demonstrate for the first time that Cr(VI) is able to induce COX-2 expression via an NFκB/c-Jun/AP-1–dependent pathway. Our results provide novel insight into the molecular mechanisms linking Cr(VI) exposure to lung inflammation and carcinogenesis.

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“…It has been reported that COX-2 transcription may be activated in cells responding to tumor promoters, growth factors, oncogenes, and cytokines via AP-1 [Zhang et al, 2008a]. Previous studies have suggested that signaling through the B1 receptor may contribute to activation of AP-1 [Naraba et al, 1998;Christiansen et al, 2002].…”

Section: Discussionmentioning

confidence: 99%

Bradykinin‐induced cell migration and COX‐2 production mediated by the bradykinin B1 receptor in glioma cells

Leung

Huang

et al. 2010

J of Cellular Biochemistry

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Bradykinin is produced and acts at the site of injury and inflammation. Recent reports have also shown that bradykinin selectively modulates blood-tumor barrier permeability. However, the molecular mechanisms and pathologic roles underlying bradykinin-induced glioma migration remain unclear. Glioma is the most common primary adult brain tumor, with a poor prognosis because of the ease with which tumor cells spread to other regions of the brain. In this study, we found that bradykinin increases the cell migration and expression of cyclo-oxygenase-2 (COX-2) in glioma cells. Bradykinin-mediated migration was attenuated by the selective COX-2 inhibitor NS-398. Moreover, increased motility of glioma cells and expression of COX-2 were mimicked by a bradykinin B1 receptor (B1R) agonist and markedly inhibited by a B1R antagonist. Bradykinin-mediated migration was attenuated by phosphoinositide 3-kinase (PI-3 kinase)/AKT inhibitors LY 294002 and wortmannin. Bradykinin stimulation also increased the phosphorylation of the p85 subunit of PI-3 kinase and serine 473 of AKT. Treatment of bradykinin with AP-1 inhibitors Tanshinone IIA and curcumin also reduced COX-2 expression and glioma cell migration. Moreover, treatment of bradykinin also induced phosphorylation of c-Jun in glioma cells. AP-1 promoter analysis in the luciferase reporter construct showed that bradykinin increased AP-1 transcription activity and was inhibited by LY 294002 and wortmannin. One mechanism underlying bradykinin-directed migration is transcriptional up-regulation of COX-2 and activation of the B1R receptor, PI-3 kinase, AKT, c-Jun, and AP-1 pathways.

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A JNK1/AP-1–Dependent, COX-2 Induction Is Implicated in 12-O-Tetradecanoylphorbol-13-Acetate–Induced Cell Transformation through Regulating Cell Cycle Progression

Abstract: Cyclooxygenase-2 (COX-

Cited by 20 publications

References 55 publications

Growth Hormone Releasing Peptide-2 Attenuation of Protein Kinase C-Induced Inflammation in Human Ovarian Granulosa Cells

Growth Hormone Releasing Peptide-2 Attenuation of Protein Kinase C-Induced Inflammation in Human Ovarian Granulosa Cells

Hexavalent Chromium Cr(VI) Up-Regulates COX-2 Expression through an NFκB/c-Jun/AP-1–Dependent Pathway

Bradykinin‐induced cell migration and COX‐2 production mediated by the bradykinin B1 receptor in glioma cells

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