title: MMPs-2 and -14 Are Elevated in Eosinophilic Esophagitis and Reduced Following Topical Corticosteroid Therapy.
abstract: OBJECTIVE
  Eosinophilic esophagitis (EoE) is a chronic, antigen-mediated disease in children and adults associated with substantial esophageal remodeling and fibrosis. The expression of the remodeling-associated matrix metalloproteinases (MMPs) has not been previously detailed in EoE.
  
  
  METHODS
  MMP-2 and -14 expression and cellular localization were assessed using real-time quantitative polymerase chain reaction and immunohistochemistry/immunofluorescence in EoE fibroblasts, active and inactive pediatric EoE biopsies, and nondiseased control biopsies. The effect of transforming growth factor (TGF)-β1 treatment on MMP-2 expression in cultured esophageal epithelial (HET1A) cells was analyzed.
  
  
  RESULTS
  MMP-2 and -14 mRNA were expressed in EoE fibroblasts and biopsies. Proliferating epithelial cells produced MMP-14 more abundantly in EoE than in controls (P < 0.001) and the degree of epithelial MMP-14 expression correlated positively with basal zone hyperplasia (r = 0.65, P = 0.002). EoE lamina propria had higher numbers of MMP-2- and -14-positive cells (906 ± 167 and 701 ± 93 cells/mm²) as compared with controls (258 ± 93 cells/mm², P < 0.01 and 232 ± 54 cells/mm², P < 0.01), and MMP-14 expression correlated with the severity of fibrosis. Following therapy with topical corticosteroids, MMP-14 and -2 were significantly diminished (P < 0.01). TGF-β1 increased the expression and secretion of MMP-2 from esophageal epithelial HET1A cells.
  
  
  CONCLUSIONS
  MMP-2 and -14 are elevated in pediatric patients with EoE and significantly decrease following topical corticosteroid therapy. TGF-β1 increases MMP-2 in esophageal epithelial cells. This alludes to previously unappreciated role for MMPs in EoE-associated esophageal remodeling and a potential positive feedback loop via TGF-β1.
authors.affiliation: *Division of Allergy, Immunology, Center for Immunity, Infection, and Inflammation †Department of Pediatrics, University of California ‡Department of Physiology and Biophysics, University of Arkansas Medical Center, Little Rock.
authors.forename: Lisa
authors.initials: L
authors.lastname: Beppu
authors.forename: Tom
authors.initials: T
authors.lastname: Yang
authors.forename: Michelle
authors.initials: M
authors.lastname: Luk
authors.forename: Robert O
authors.initials: RO
authors.lastname: Newbury
authors.forename: Jacob
authors.initials: J
authors.lastname: Palmquist
authors.forename: Ranjan
authors.initials: R
authors.lastname: Dohil
authors.forename: Richard C
authors.initials: RC
authors.lastname: Kurten
authors.forename: David H
authors.initials: DH
authors.lastname: Broide
authors.forename: Seema S
authors.initials: SS
authors.lastname: Aceves
mesh_terms: D000305:Adrenal Cortex Hormones / Q000627:therapeutic use*; D001706:Biopsy; D002648:Child; D057765:Eosinophilic Esophagitis / Q000188:drug therapy / Q000201:enzymology* / Q000473:pathology; D004847:Epithelial Cells / Q000201:enzymology / Q000473:pathology; D005260:Female; D005347:Fibroblasts / Q000201:enzymology; D005455:Fluorescent Antibody Technique; D015870:Gene Expression / Q000187:drug effects; D006801:Humans; D007150:Immunohistochemistry; D008297:Male; D053511:Matrix Metalloproteinase 14 / Q000032:analysis* / Q000187:drug effects / Q000235:genetics; D020778:Matrix Metalloproteinase 2 / Q000032:analysis* / Q000187:drug effects / Q000235:genetics; D012333:RNA, Messenger / Q000032:analysis; D060888:Real-Time Polymerase Chain Reaction; D053773:Transforming Growth Factor beta1 / Q000494:pharmacology
chemical_list: D000305:Adrenal Cortex Hormones; D012333:RNA, Messenger; D053773:Transforming Growth Factor beta1; D020778:Matrix Metalloproteinase 2; D053511:Matrix Metalloproteinase 14