DNA promoter methylation status and protein expression of interleukin-8 in human colorectal adenocarcinomas

Abstract

BackgroundInterleukin-8 (IL-8) also referred to as CXCL8, a member of the CXC chemokine family that attracts neutrophils and other leukocytes, has been associated with cancer. Angiogenesis is a prime regulator of tumour expansion and data support that IL-8 is a potent angiogenic factor. Epigenomic instability has been postulated to play a role for the development of multiple neoplasias including colorectal cancer (CRC). DNA methylation of cytosine residues in CpG dinucleotides leads to transcriptional silencing of associated genes.MethodIn this study, we comparatively analysed the protein expression of IL-8 in plasma, tumour and paired normal tissue and methylation status of the IL-8 gene to evaluate its impact on CRC.ResultsCollectively, by using Luminex technology, we noted a significantly higher IL-8 level in cancer tissue compared to paired normal tissue and that CRC patients exhibit significantly higher plasma levels than healthy controls. Analysed by methylation-specific polymerase chain reaction, we detected IL-8 hypomethylation in 64% of the cancerous tissue cases but no hypomethylation was found in paired normal tissue. We noted that the CRC patients with IL-8 hypomethylation revealed a significant higher level of IL-8 protein in cancerous tissue, which tended to be associated with distant metastasis. We also observed that patients with distant metastasis showed a significantly higher plasma level of IL-8 in relation to patients without distant metastasis.ConclusionOur results suggest that the predominance of high plasma levels of IL-8 in patients with distant metastasis in combination with the hypomethylation of the IL-8 promoter region might be a useful marker of the disease advancement.

PGE2 inducesinterleukin-8derepression in human astrocytoma through coordinated DNA demethylation and histone hyperacetylation

“…However, in contrast to the elucidation of the cis element and trans factors involved in the transcriptional control of this gene, the evidence for the participation of epigenetic mechanisms was only partially revealed, and contrasting results were sometimes obtained. In this regard, a marked CpG hypomethylation of the IL-8 promoter has been detected in human colorectal adenocarcinomas 29 and in aggressive and chronic periodontitis, 30 , 31 whereas other studies have proved that atypical methylation pattern of the IL-8 promoter strongly correlates with an increase in IL-8 expression and the metastatic potential of breast carcinoma cells 32 . A larger number of studies have been conducted to determine histone modifications associated with IL-8 gene expression following a variety of stimuli, such as LPS in intestinal epithelial cells, 33 leptin in synovial fibroblast cells, 34 UVR in keratinocytes 35 and Moraxella catarrhalis in bronchial epithelial cells 36 .…”

Arsenic exposure causes epigenetic dysregulation of IL-8 expression leading to proneoplastic changes in kidney cells

“…The hypomethylated six CpG sites in the IL-8 promoter have been associated with renal cell carcinoma (Yoo et al, 2013). Earlier study have also shown the role of IL-8 methylation in oral epithelial cells of aggressive and chronic periodontitis and in human colorectal adenocarcinomas (Andia et al, 2010;Oliveira et al, 2009;Dimberg et al, 2012).…”

“…The bisulfite converted DNA was amplified using specific MSP primers (IL-8 MF (c-f), IL-8 MR(c-f), IL-8 UMF(cf) and IL-8 UMR(c-f) ( Table 2) (Dimberg et al, 2012). All the primers were synthesized commercially through IDT, USA.…”

CXCL8, IL-1β and sCD200 are pro-inflammatory cytokines and their levels increase in the circulation of breast carcinoma patients

“…Previous studies have shown that CXCL8 and its receptors, CXCR1 and CXCR2, were significantly upregulated in colorectal cancers and acted as regulators of proliferation, angiogenesis and metastasis (2-4). Dimberg et al (5) reported that high plasma levels of CXCL8 tend to be correlated with distant metastasis, indicating an advanced disease stage. Thus far, the serum level of CXCL8 in patients with breast carcinoma has not been investigated extensively.…”