title: Inhibiting interleukin-19 activity ameliorates esophageal squamous cell carcinoma progression.
abstract: BACKGROUND
  IL-19 is expressed in esophageal squamous cell carcinoma (SCC), but its biological effect on esophageal cancer remains unclear. We determined the correlation between IL-19 expression levels and clinicopathological variables and explored the effects of IL-19 on the esophageal SCC in vivo and in vitro.
  
  
  RESULTS
  We determined the expression levels of esophageal SCC tissues from 60 patients using immunohistochemistry. We examined the effects of IL-19 on intracellular signaling, cytokines production as well as proliferation, colonization, and migration in the human esophageal SCC cell line CE81T. Monoclonal antibodies (mAbs) against IL-19 (1BB1) and its receptor IL-20R1 (51D) were used to antagonize the effects of IL-19. We injected SCID mice with CE81T cells and then treated them with anti-IL-19 mAb or control IgG every 3 days and determined tumor growth for 32 days. Of the 60 esophageal SCC patients, 36 patients (60%) were IL-19 strongly stained, which was associated with advanced tumor stage. CE81T cells expressed IL-19 and its receptors. IL-19 induced phosphorylation of STAT3, P38, JNK, ERK1/2, Akt, and NF-κB in CE81T cells. IL-19 promoted the proliferation, colonization, and migration of CE81T cells, which were antagonized by 1BB1 and 51D. IL-19 also induced expression of the transcripts of TGF-β, cyclin B1, CXCR4, and MMP-1 in CE81T cells. In CE81T tumor-bearing mice, 1BB1 reduced tumor growth and downregulated TGF-β, cyclin B1, MMP-1, and CXCR4 expression in tumors.
  
  
  CONCLUSIONS
  IL-19 affects the pathogenesis of esophageal cancer. IL-19 mAb (1BB1) is potentially a potent drug for esophageal cancer therapy.
authors.affiliation: Department of Anesthesiology, Chi-Mei Medical Center, Tainan, Taiwan ; Department of Anesthesiology, College of Medicine, Taipei Medical University, Taipei, Taiwan.
authors.forename: Chung-Hsi
authors.initials: CH
authors.lastname: Hsing
authors.forename: Franky Antonius
authors.initials: FA
authors.lastname: Kwok
authors.forename: Hung-Chi
authors.initials: HC
authors.lastname: Cheng
authors.forename: Chien-Feng
authors.initials: CF
authors.lastname: Li
authors.forename: Ming-Shi
authors.initials: MS
authors.lastname: Chang
mesh_terms: D000818:Animals; D000911:Antibodies, Monoclonal / Q000627:therapeutic use; D002294:Carcinoma, Squamous Cell / Q000188:drug therapy / Q000378:metabolism*; D002465:Cell Movement / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects; D004938:Esophageal Neoplasms / Q000188:drug therapy / Q000378:metabolism*; D000077277:Esophageal Squamous Cell Carcinoma; D006801:Humans; D066298:In Vitro Techniques; D007378:Interleukins / Q000037:antagonists & inhibitors / Q000378:metabolism* / Q000494:pharmacology*; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D016513:Mice, SCID; D060888:Real-Time Polymerase Chain Reaction; D018123:Receptors, Interleukin / Q000378:metabolism; D012189:Retrospective Studies
chemical_list: D000911:Antibodies, Monoclonal; C421250:IL19 protein, human; D007378:Interleukins; D018123:Receptors, Interleukin; C492510:interleukin-20 receptor