Regulation of Interleukin-8 Expression by Cellular pH in Human Pancreatic Adenocarcinoma Cells

Shi, Qian; Xin, Le; Wang, Bailiang; Xiong, Qinghua; Abbruzzese, James L.; Xie, Keping

doi:10.1089/10799900050198471

Cited by 58 publications

(52 citation statements)

References 18 publications

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“…Acidosis has been reported to potentiate the expression of several proinflammatory genes (31,32). Consistent with this, we observed a trend for increased TNF␣ mRNA and COX-2 protein expression at more acid pH e (Fig.…”

Section: Discussionsupporting

confidence: 89%

Hypercapnia Induces Cleavage and Nuclear Localization of RelB Protein, Giving Insight into CO2 Sensing and Signaling

Oliver

Lenihan

Brüning

et al. 2012

Journal of Biological Chemistry

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Background: The molecular mechanisms underpinning how CO 2 affects cell signaling and gene transcription are not well understood.Results: The NF-B family member RelB is cleaved and translocates to the nucleus of cells in response to elevated CO 2 (hypercapnia). Conclusion:The NF-B signaling pathway is affected by CO 2 . Significance: This study provides new molecular insight into modulation of inflammatory pathways under conditions of hypercapnia.

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Section: Discussionsupporting

confidence: 89%

Hypercapnia Induces Cleavage and Nuclear Localization of RelB Protein, Giving Insight into CO2 Sensing and Signaling

Oliver

Lenihan

Brüning

et al. 2012

Journal of Biological Chemistry

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“…Metabolic imbalance between vascularization and tumor formation in aggressive pancreatic cancer could lead to low blood flow and low extracellular pH in tumor microenvironment. Hypoxia and acidosis enhanced expression of CXCL-8 by activation of NF-κB and AP-1 in pancreatic cancer cells (14).…”

Section: Discussionmentioning

confidence: 97%

Induction of interleukin-8 (CXCL-8) by tumor necrosis factor-α and leukemia inhibitory factor in pancreatic carcinoma cells: Impact of CXCL-8 as an autocrine growth factor

Kamohara

Takahashi²,

Ishiko³

et al. 2007

Int J Oncol

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Abstract. Pancreatic carcinoma is one of the most lethal of the gastrointestinal malignant tumors. Chronic inflammation leads to cancer development and progression. Interleukin-8 (CXCL-8) is a CXC chemokine, which plays an important role in neutrophil chemotaxis and activation. We previously reported that CXCL-8 was produced by a variety of human carcinoma cells and tissues, and that CXCL-8 promoted proliferation in pancreatic carcinoma cells (SUIT-2). In the present study, we analyzed whether various cytokines affect cell proliferation by CXCL-8 expression in pancreas carcinoma cells. All examined pancreatic carcinoma cells expressed CXCL-8 and TNFRII mRNA constitutively in RPMI-1640 medium without FBS. TNF-α, LIF, IL-1ß, IL-6, IL-8, or IFN-ß enhanced the expression of CXCL-8 mRNA, but IL-10 did not in Hs-700T cells. Actinomycin D suppressed and cycloheximide augmented CXCL-8 mRNA which was induced by TNF-α or not. The half-life of CXCL-8 mRNA was 36.5 min by TNF-α and 35.2 min by no stimulation. In our previous study, LIF promoted cell growth in Hs-700T cells. LIF induced CXCL-8 mRNA in a dose-and time-dependent manner. Addition of recombinant CXCL-8 did not induce cell growth of Hs-700T. Anti-CXCL-8 IgG significantly suppressed cell growth. CXCL-8 would act as an autocrine growth factor in Hs-700T cells, which expressed CXCL-8 mRNA highly without stimulation. Curcumin (diferuloylmethane), NF-κB inhibitor, suppressed cell proliferation in Hs-700T cells. These results suggest that CXCL-8 plays a pivotal role in progression of pancreatic cancer, and its expression is influenced by inflammatory cytokines in pancreatic tumor microenvironment.

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“…We established a link between tumor acidic pH and VEGF up-regulation in U87 MG human glioma cells. Acidic pH has been shown to up-regulate VEGF and basic fibroblast growth factor expression in human endothelial cells (29) and various tumor cells (15,30), as well as interleukin-8 expression in human ovarian carcinoma cells (31) and in human pancreatic cancer cells (32). On the other hand, some studies also show that acidic pH decreases the expression of VEGF and extracellular matrix proteins gene expression in mouse osteoblasts (33,34).…”

Section: Discussionmentioning

confidence: 99%

Acidic Extracellular pH Induces Vascular Endothelial Growth Factor (VEGF) in Human Glioblastoma Cells via ERK1/2 MAPK Signaling Pathway

Fukumura

Jain

2002

Journal of Biological Chemistry

255

197

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Overexpression of vascular endothelial growth factor (VEGF) is associated with disease progression in human glioblastomas. We recently showed that VEGF promoter activity is inversely correlated with tumor extracellular pH (pH o ) in vivo in the human glioma (U87 MG) xenografts. Here we show that substitution of the neutral culture medium (pH 7.3) with acidic pH medium (pH 6.6) up-regulates VEGF mRNA and protein production in human glioblastoma cells as reflected by Northern blot analysis and enzyme-linked immunosorbent assay. Functional analysis of the VEGF promoter reveals that the sequence between ؊961 bp and ؊683 bp upstream of the transcription start site is responsible for the transcriptional activation of the VEGF gene by acidic pH. This region contains the binding site for AP-1. Consequently, AP-1 luciferase reporter gene was activated by acidic pH. Gel-shift analysis confirmed that AP-1 DNA binding activity is induced under acidic pH. While investigating the upstream signaling pathways, we found that ERK1/2 MAPK is activated and translocates to the nucleus to activate Elk-1, and inhibition of the activation of ERK by specific inhibitors of MEK1 blocks the up-regulation of VEGF by low pH. Dominant negative forms of Ras and Raf abolished the activation of VEGF promoter by acidic pH. These results show that acidic pH activates Ras and the ERK1/2 MAPK pathway to enhance VEGF transcription via AP-1, leading to increased VEGF production.

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Regulation of Interleukin-8 Expression by Cellular pH in Human Pancreatic Adenocarcinoma Cells

Cited by 58 publications

References 18 publications

Hypercapnia Induces Cleavage and Nuclear Localization of RelB Protein, Giving Insight into CO2 Sensing and Signaling

Hypercapnia Induces Cleavage and Nuclear Localization of RelB Protein, Giving Insight into CO2 Sensing and Signaling

Induction of interleukin-8 (CXCL-8) by tumor necrosis factor-α and leukemia inhibitory factor in pancreatic carcinoma cells: Impact of CXCL-8 as an autocrine growth factor

Acidic Extracellular pH Induces Vascular Endothelial Growth Factor (VEGF) in Human Glioblastoma Cells via ERK1/2 MAPK Signaling Pathway

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