title: Prostaglandin E2 inhibits migration of colonic lamina propria fibroblasts.
abstract: BACKGROUND
  Migration of colonic lamina propria fibroblasts (CLPF) is an important mechanism during wound healing in inflammatory bowel disease (IBD). The concentration of prostaglandin E2 (PGE2) is increased in the intestinal mucosa of IBD patients. We therefore investigated the role of PGE2 in CLPF migration.
  
  
  METHODS
  Primary cultures of CLPF were isolated from healthy controls and Crohn's disease patients. Migration assays were performed in the Boyden chamber and scratch assays. EP receptors, PGE2, intracellular cyclic adenosine monophosphate (cAMP), expression and distribution of F-actin, alpha-smooth muscle actin (SMA), and myosin light chain (MLC) were determined by immunoblotting, immunocytochemistry, and enzyme-linked immunosorbent assay (ELISA).
  
  
  RESULTS
  All four EP receptor subtypes were present on CLPF. PGE2 and agonists to the EP2 and EP4 receptor reduced the migration of CLPF. Blockade of the EP2 and the EP4 receptor inhibited the effect of PGE2 on CLPF migration. An increase in intracellular cAMP reduced CLPF migration. PGE2 increased the concentrations of cAMP in CLPF, with abrogation after addition of EP2 and EP4 receptor antagonists. PGE2 and forskolin decreased the expression of alpha-SMA and F-actin and reduced cell polarization and lamellipodium formation in a scratch assay. In addition, forskolin reduced the phosphorylation of MLC (pMLC) and led to lack of accumulation of pMLC in the leading edge of CLPF.
  
  
  CONCLUSIONS
  PGE2 reduced the migration of CLPF via elevation of intracellular cAMP. Potential mechanisms are changes in expression of cytoskeletal proteins, failure of CLPF to polarize, and a decreased amount of pMLC. This might be a possible reason for the impairment of intestinal wound healing in IBD.
authors.affiliation: Department of Internal Medicine I, University of Regensburg, Regensburg, Germany. florian.rieder@t-online.de
authors.forename: Florian
authors.initials: F
authors.lastname: Rieder
authors.forename: Martina
authors.initials: M
authors.lastname: Georgieva
authors.forename: Anja
authors.initials: A
authors.lastname: Schirbel
authors.forename: Monika
authors.initials: M
authors.lastname: Artinger
authors.forename: Anita
authors.initials: A
authors.lastname: Zügner
authors.forename: Martin
authors.initials: M
authors.lastname: Blank
authors.forename: Julia
authors.initials: J
authors.lastname: Brenmoehl
authors.forename: Jürgen
authors.initials: J
authors.lastname: Schölmerich
authors.forename: Gerhard
authors.initials: G
authors.lastname: Rogler
mesh_terms: D015153:Blotting, Western; D002465:Cell Movement / Q000187:drug effects*; D002478:Cells, Cultured; D003106:Colon / Q000166:cytology* / Q000187:drug effects* / Q000378:metabolism; D000242:Cyclic AMP / Q000378:metabolism; D015232:Dinoprostone / Q000494:pharmacology*; D005347:Fibroblasts / Q000166:cytology* / Q000187:drug effects / Q000378:metabolism; D005455:Fluorescent Antibody Technique; D006801:Humans; D009092:Mucous Membrane / Q000166:cytology* / Q000187:drug effects / Q000378:metabolism; D010120:Oxytocics / Q000494:pharmacology*; D058306:Receptors, Prostaglandin E, EP1 Subtype / Q000378:metabolism; D058307:Receptors, Prostaglandin E, EP2 Subtype / Q000378:metabolism; D058308:Receptors, Prostaglandin E, EP3 Subtype / Q000378:metabolism; D058309:Receptors, Prostaglandin E, EP4 Subtype / Q000378:metabolism; D014945:Wound Healing / Q000187:drug effects
chemical_list: D010120:Oxytocics; C545635:PTGER1 protein, human; C545644:PTGER2 protein, human; C545647:PTGER3 protein, human; D058306:Receptors, Prostaglandin E, EP1 Subtype; D058307:Receptors, Prostaglandin E, EP2 Subtype; D058308:Receptors, Prostaglandin E, EP3 Subtype; D058309:Receptors, Prostaglandin E, EP4 Subtype; D000242:Cyclic AMP; D015232:Dinoprostone