title: ApoE deficiency promotes colon inflammation and enhances inflammatory potential oxidized-LDL and TNF-α in colon epithelial cells.
abstract: 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.
authors.affiliation: LSUHSC, 1700 Tulane Ave, Kenner, Louisiana, 70065, United States.
authors.forename: Ali
authors.initials: A
authors.lastname: El-Bahrawy
authors.affiliation: LSUHSC, 1700 Tulane Ave, Kenner, Louisiana, 70065, United States.
authors.forename: Abdelmetalab
authors.initials: A
authors.lastname: Tarhuni
authors.affiliation: The Stanley Scott Cancer Center, LSU Health Science Center, 533 Bolivar St, New Orleans, Louisiana, 70112, United States.
authors.forename: Hogyoung
authors.initials: H
authors.lastname: Kim
authors.affiliation: LSUHSC, 1700 Tulane Ave, Kenner, Louisiana, 70065, United States.
authors.forename: Venkat
authors.initials: V
authors.lastname: Subramaniam
authors.affiliation: LSUHSC, 1700 Tulane Ave, Kenner, Louisiana, 70065, United States.
authors.forename: Ilyes
authors.initials: I
authors.lastname: Benslimane
authors.affiliation: Tulane Univ, 1700 Tulane Ave, New Orleans, Louisiana, 70112, United States.
authors.forename: Zakaria Y
authors.initials: ZY
authors.lastname: Abd Elmageed
authors.affiliation: LSUHSC, 1700 Tulane Ave, Kenner, Louisiana, 70065, United States.
authors.forename: Samuel
authors.initials: S
authors.lastname: Okpechi
authors.affiliation: LSUHSC, 1700 Tulane Ave, Kenner, Louisiana, 70065, United States.
authors.forename: Mohamed
authors.initials: M
authors.lastname: Ghonim
authors.affiliation: Al-Azhar Un iversity, Assiut, Egypt.
authors.forename: Ramadan
authors.initials: R
authors.lastname: Hemeida
authors.affiliation: Al-Azhar Un iversity, Beni-Suef City, Arizona, Egypt.
authors.forename: Amira
authors.initials: A
authors.lastname: Abo-Yousef
authors.affiliation: Al-Azhar Un iversity, Kafr El-Sheikh, Egypt.
authors.forename: Gamal
authors.initials: G
authors.lastname: El-Sherbiny
authors.affiliation: Al-Azhar Un iversity, Assiut, Egypt.
authors.forename: Ihab
authors.initials: I
authors.lastname: Abdel-Raheem
authors.affiliation: LSUHSC, 1700 Tulane Ave, Kenner, Louisiana, 70065, United States.
authors.forename: Jong
authors.initials: J
authors.lastname: Kim
authors.affiliation: The Stanley Scott Cancer Center, LSU Health Science Center, 533 Bolivar St, New Orleans, Louisiana, 70112, United States.
authors.forename: Amarjit S
authors.initials: AS
authors.lastname: Naura
authors.affiliation: LSUHSC, 1700 Tulane Ave, Kenner, Louisiana, 70065, United States hboulr@lsuhsc.edu.
authors.forename: Hamid
authors.initials: H
authors.lastname: Boulares
keywords: ApoE; colon; inflammation; nuclear factor kappaB; tumour necrosis factors