title: Effect of PIP3 on adhesion molecules and adhesion of THP-1 monocytes to HUVEC treated with high glucose.
abstract: BACKGROUND
  Phosphatidylinositol-3,4,5-triphosphate (PIP3), a well-known lipid second messenger, plays a key role in insulin signaling and glucose homeostasis. Using human umbilical vein endothelial cells (HUVEC) and THP-1 monocytes, we tested the hypothesis that PIP3 can downregulate adhesion molecules and monocyte adhesion to endothelial cells.
  
  
  METHODS
  HUVEC and monocytes were exposed to high glucose (HG, 25 mM, 20 h) with or without PIP3 (0-20 nM), or PIT-1 (25 µM), an inhibitor of PIP3.
  
  
  RESULTS
  Both HG and PIT-1 caused a decrease in cellular PIP3 in monocytes and HUVEC compared to controls. Treatment with PIT-1 and HG also increased the ICAM-1 (intercellular adhesion molecule 1) total protein expression as well as its surface expression in HUVEC, CD11a (a subunit of lymphocyte function-associated antigen 1, LFA-1) total protein expression as well as its surface expression in monocytes, and adhesion of monocytes to HUVEC. Exogenous PIP3 supplementation restored the intracellular PIP3 concentrations, downregulated the expression of adhesion molecules, and reduced the adhesion of monocytes to HUVEC treated with HG.
  
  
  CONCLUSIONS
  This study reports that a decrease in cellular PIP3 is associated with increased expression of adhesion molecules and monocyte-endothelial cell adhesion, and may play a role in the endothelial dysfunction associated with diabetes.
authors.affiliation: Department of Pediatrics, Louisiana State University Health Sciences Center, Shreveport, USA.
authors.forename: Prasenjit
authors.initials: P
authors.lastname: Manna
authors.forename: Sushil K
authors.initials: SK
authors.lastname: Jain
mesh_terms: D040881:CD11a Antigen / Q000378:metabolism; D002448:Cell Adhesion / Q000187:drug effects*; D015815:Cell Adhesion Molecules / Q000378:metabolism*; D002460:Cell Line; D015536:Down-Regulation; D005947:Glucose / Q000494:pharmacology*; D061307:Human Umbilical Vein Endothelial Cells; D006801:Humans; D018799:Intercellular Adhesion Molecule-1 / Q000378:metabolism; D009000:Monocytes / Q000166:cytology / Q000378:metabolism; D018129:Phosphatidylinositol Phosphates / Q000494:pharmacology*; D011994:Recombinant Proteins / Q000096:biosynthesis / Q000235:genetics / Q000494:pharmacology; D050817:Transcription Factor Pit-1 / Q000235:genetics / Q000378:metabolism / Q000494:pharmacology
chemical_list: D040881:CD11a Antigen; D015815:Cell Adhesion Molecules; D018129:Phosphatidylinositol Phosphates; D011994:Recombinant Proteins; D050817:Transcription Factor Pit-1; C060974:phosphatidylinositol 3,4,5-triphosphate; D018799:Intercellular Adhesion Molecule-1; D005947:Glucose
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