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.