title: Vibrio parahaemolyticus infection induces modulation of IL-8 secretion through dual pathway via VP1680 in Caco-2 cells.
abstract: BACKGROUND
  Vibrio parahaemolyticus causes acute gastroenteritis and inflammations in humans. A variety of pathogenic bacteria can stimulate mitogen-activated protein kinases (MAPKs) in host cells. Phosphorylation of MAPKs leads to production of interleukin (IL)- 8 and subsequently causes inflammations. Thus, MAPK cascades were strong candidates for the main signaling pathway of V. parahaemolyticus-induced acute inflammation.
  
  
  METHODS
  To determine whether the signaling pathway on V. parahaemolyticus infection induces inflammation, we analyzed the secretion level of IL-8 and phosphorylation of MAPKs by use of intestinal epithelial Caco-2 cells.
  
  
  RESULTS
  V. parahaemolyticus infection of Caco-2 cells activated extracellular signal-regulated kinase (ERK) 1/2 and p38 MAPK signal pathways, leading to IL-8 secretion, whereas MAPK inhibitors, UO126 or SB203580, suppressed IL-8 secretion. A strain carrying a deletion of VP1680, a type three secretion system 1 (T3SS1) effector protein, failed to activate phosphorylation of ERK1/2 and p38 MAPK and secretion of IL-8. ERK1/2 pathway inhibitor, UO126, failed IL-8 promoter activity, whereas p38 MAPK inhibitor, SB203580, decreased the stabilization of IL-8 messenger RNA following V. parahaemolyticus infection.
  
  
  CONCLUSIONS
  We showed that V. parahaemolyticus infection of Caco-2 cells results in the secretion of IL-8, and that VP1680 plays a pivotal role in manipulating host cell signaling and is responsible for triggering IL-8 secretion.
authors.affiliation: Department of Preventive Environment and Nutrition, Institute of Health Biosciences, University of Tokushima Graduate School, Tokushima, Japan.
authors.forename: Takaaki
authors.initials: T
authors.lastname: Shimohata
authors.forename: Masayuki
authors.initials: M
authors.lastname: Nakano
authors.forename: Xin
authors.initials: X
authors.lastname: Lian
authors.forename: Tomomi
authors.initials: T
authors.lastname: Shigeyama
authors.forename: Hitomi
authors.initials: H
authors.lastname: Iba
authors.forename: Akiko
authors.initials: A
authors.lastname: Hamamoto
authors.forename: Masaki
authors.initials: M
authors.lastname: Yoshida
authors.forename: Nagakatsu
authors.initials: N
authors.lastname: Harada
authors.forename: Hironori
authors.initials: H
authors.lastname: Yamamoto
authors.forename: Masayuki
authors.initials: M
authors.lastname: Yamato
authors.forename: Kazuaki
authors.initials: K
authors.lastname: Mawatari
authors.forename: Toshiaki
authors.initials: T
authors.lastname: Tamaki
authors.forename: Yutaka
authors.initials: Y
authors.lastname: Nakaya
authors.forename: Akira
authors.initials: A
authors.lastname: Takahashi
mesh_terms: D018938:Caco-2 Cells; D006801:Humans; D016209:Interleukin-8 / Q000378:metabolism*; D020928:Mitogen-Activated Protein Kinases / Q000378:metabolism*; D010766:Phosphorylation; D015398:Signal Transduction; D014736:Vibrio parahaemolyticus / Q000276:immunology* / Q000472:pathogenicity*; D014764:Viral Proteins / Q000276:immunology*; D037521:Virulence Factors / Q000276:immunology*
chemical_list: D016209:Interleukin-8; D014764:Viral Proteins; D037521:Virulence Factors; D020928:Mitogen-Activated Protein Kinases