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

Although deficiency in Apolipoprotein E (ApoE) is linked to many diseases, its effect on colon homeostasis remains unknown.  ApoE appears to control inflammation by regulating NF-kB.  This 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, this study also examined whether such deficiency enhances the inflammatory potential of oxidized-LDL (oxLDL) and TNF-α, in colon epithelial cells 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-a to induce COX-2 expression as well as several other inflammatory factors in primary colon epithelial cells.   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, 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 homeostasis and that ApoE deficiency may constitute a risk factor for colon pathologies.