ApoE deficiency promotes colon inflammation and enhances the inflammatory potential of oxidized-LDL and TNF-α in primary colon epithelial cells

Abstract

Although deficiency in Apolipoprotein E (ApoE) is linked to many diseases, its effect on colon homoeostasis remains unknown. ApoE appears to control inflammation by regulating nuclear factor-κB (NF-κB). The present study was designed to examine whether ApoE deficiency affects factors of colon integrity in vivo and given the likelihood that ApoE deficiency increases oxidized lipids and TNF-α, the present study also examined whether such deficiency enhances the inflammatory potential of oxidized-LDL (oxLDL) and TNF-α in colon epithelial cells (CECs), in vitro. Here we show that ApoE deficiency is associated with chronic inflammation systemically and in colonic tissues as assessed by TNF-α levels. Increased colon TNF-α mRNA coincided with a substantial increase in cyclooxygenase (COX)-2. ApoE deficiency enhanced the potential of oxLDL and TNF-α to induce COX-2 expression as well as several other inflammatory factors in primary CECs. Interestingly, oxLDL enhanced TGF-β expression only in ApoE−/−, but not in wild-type, epithelial cells. ApoE deficiency appears to promote COX-2 expression enhancement through a mechanism that involves persistent NF-κB nuclear localization and PI3 and p38 MAP kinases but independently of Src. In mice, ApoE deficiency promoted a moderate increase in crypt length, which was associated with opposing effects of an increase in cell proliferation and apoptosis at the bottom and top of the crypt respectively. Our results support the notion that ApoE plays a central role in colon homoeostasis and that ApoE deficiency may constitute a risk factor for colon pathologies.

Clinical Assay for the Early Detection of Colorectal Cancer Using Mass Spectrometric Wheat Germ Agglutinin Multiple Reaction Monitoring

“…A study by Buss et al showed that APOE −/− breast cancer tumors grew faster than controls in mouse experiments, which indicates that APOE may inhibit cancer development [ 73 ]. Moreover, EI-Bahrawy et al suggested that APOE plays an important role in metabolism in the colon; the absence of APOE can stimulate the expression of cyclooxygenase (COX)-2 by increasing oxidized low-density lipoprotein (Ox-LDL) and tumor necrosis factor (TNF)-α, which induces inflammation and results in colon disease [ 74 ]. Also, APOE was observed to have decreased in lung cancer tissues [ 75 ].…”

Bik reduces hyperplastic cells by increasing Bak and activating DAPk1 to juxtapose ER and mitochondria

“…Primary HAECs were purchased from Cambrex Bio Science Walkersville, Inc (Walkersville, MD). Primary murine colon epithelial cells were isolated from 4 -weeks-old C57BL/6 mice 63 . Briefly, intestinal contents were cleaned and colons were flushed with cold PBS.…”

Apolipoprotein E Overexpression Is Associated With Tumor Progression and Poor Survival in Colorectal Cancer

“…In lung adenocarcinoma, ApoE over-expression promotes cancer proliferation and migration and is related to chemo-resistance (Su et al, 2011). A recent study implicated the ApoE moderates the colon homeostasis and constitutes a risk factor for colon pathologies (El-Bahrawy et al, 2016). However, the prognostic value of ApoE expression for CRC remains unclear, and to the best of our knowledge, although some previous research has been implicated that APOE might influence CRC development through three potential path ways: cholesterol and bile metabolism, triglyceride and insulin regulation, and the prolonged inflammation (Slattery et al, 2005; Mrkonjic et al, 2009; Kato et al, 2010), there has not been a prior study of functional expression and prognostic significance for CRC.…”