title: Downregulation of CPI-17 contributes to dysfunctional motility in chronic intestinal inflammation model mice and ulcerative colitis patients.
abstract: BACKGROUND
  Chronic intestinal inflammation is frequently accompanied by motility disorders. We previously reported that proinflammatory cytokines, such as tumor necrosis factor alpha and interleukin (IL)-1beta downregulate CPI-17, an endogenous inhibitor of serine/threonine protein phosphatase in smooth-muscle cells, which results in the inhibition of myosin light chain phosphorylation and contractility. However, its clinical relevance has not been clarified.
  
  
  METHODS
  The present study examined the changes in CPI-17 expression in chronic intestinal inflammation using smooth-muscle tissues from IL-10 knockout mice and from patients with ulcerative colitis (UC).
  
  
  RESULTS
  The IL-10 knockout mice developed spontaneous and chronic colitis accompanied by immune cell infiltration, submucosal fibrosis, and thickening of the muscularis externa. The expression of alpha-smooth muscle actin protein in the smooth-muscle layer did not change, whereas that of CPI-17 protein was decreased by about 40% compared with healthy wild-type controls. Consistent with this observation, smooth-muscle contractile force and myosin light chain phosphorylation induced by a muscarinic agonist were reduced in the knockout mice. Moreover, we observed that CPI-17 protein expression was decreased in smooth-muscle tissues from patients with UC compared with controls.
  
  
  CONCLUSIONS
  CPI-17 downregulation might contribute to the decreased motor function in chronic inflammatory bowel diseases.
authors.affiliation: Department of Veterinary Pharmacology, Graduate School of Agriculture and Life Sciences, The University of Tokyo, 1-1-1 Yayoi, Bunkyo-ku, Tokyo 113-8657, Japan.
authors.forename: Takashi
authors.initials: T
authors.lastname: Ohama
authors.forename: Masatoshi
authors.initials: M
authors.lastname: Hori
authors.forename: Masahiko
authors.initials: M
authors.lastname: Fujisawa
authors.forename: Masaharu
authors.initials: M
authors.lastname: Kiyosue
authors.forename: Masaki
authors.initials: M
authors.lastname: Hashimoto
authors.forename: Yuka
authors.initials: Y
authors.lastname: Ikenoue
authors.forename: Yoshio
authors.initials: Y
authors.lastname: Jinno
authors.forename: Hiroto
authors.initials: H
authors.lastname: Miwa
authors.forename: Takayuki
authors.initials: T
authors.lastname: Matsumoto
authors.forename: Takahisa
authors.initials: T
authors.lastname: Murata
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Ozaki
mesh_terms: D000818:Animals; D015153:Blotting, Western; D003093:Colitis, Ulcerative / Q000378:metabolism* / Q000473:pathology / Q000503:physiopathology; D003106:Colon / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology; D004195:Disease Models, Animal; D015536:Down-Regulation; D004591:Electrophoresis, Polyacrylamide Gel; D005769:Gastrointestinal Motility / Q000502:physiology*; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009124:Muscle Proteins / Q000096:biosynthesis*; D009129:Muscle Tonus / Q000502:physiology; D009130:Muscle, Smooth / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology; D010749:Phosphoprotein Phosphatases / Q000037:antagonists & inhibitors / Q000096:biosynthesis*; D010750:Phosphoproteins / Q000096:biosynthesis*
chemical_list: D047908:Intracellular Signaling Peptides and Proteins; D009124:Muscle Proteins; C107507:PPP1R14A protein, human; D010750:Phosphoproteins; C491520:Ppp1r14a protein, mouse; D010749:Phosphoprotein Phosphatases