title: MAPK Activation Is Essential for Waddlia chondrophila Induced CXCL8 Expression in Human Epithelial Cells.
abstract: BACKGROUND
  Waddlia chondrophila (W. chondrophila) is an emerging agent of respiratory and reproductive disease in humans and cattle. The organism is a member of the order Chlamydiales, and shares many similarities at the genome level and in growth studies with other well-characterised zoonotic chlamydial agents, such as Chlamydia abortus (C. abortus). The current study investigated the growth characteristics and innate immune responses of human and ruminant epithelial cells in response to infection with W. chondrophila.
  
  
  METHODS
  Human epithelial cells (HEp2) were infected with W. chondrophila for 24h. CXCL8 release was significantly elevated in each of the cell lines by active-infection with live W. chondrophila, but not by exposure to UV-killed organisms. Inhibition of either p38 or p42/44 MAPK significantly inhibited the stimulation of CXCL8 release in each of the cell lines. To determine the pattern recognition receptor through which CXCL8 release was stimulated, wild-type HEK293 cells which express no TLR2, TLR4, NOD2 and only negligible NOD1 were infected with live organisms. A significant increase in CXCL8 was observed.
  
  
  CONCLUSIONS
  W. chondrophila actively infects and replicates within both human and ruminant epithelial cells stimulating CXCL8 release. Release of CXCL8 is significantly inhibited by inhibition of either p38 or p42/44 MAPK indicating a role for this pathway in the innate immune response to W. chondrophila infection. W. chondrophila stimulation of CXCL8 secretion in HEK293 cells indicates that TLR2, TLR4, NOD2 and NOD1 receptors are not essential to the innate immune response to infection.
authors.affiliation: Moredun Research Institute, Pentlands Science Park, Edinburgh, Midlothian, EH26 0PZ, United Kingdom.
authors.forename: Skye
authors.initials: S
authors.lastname: Storrie
authors.affiliation: Moredun Research Institute, Pentlands Science Park, Edinburgh, Midlothian, EH26 0PZ, United Kingdom.
authors.forename: David
authors.initials: D
authors.lastname: Longbottom
authors.affiliation: School of Life, Sport and Social Sciences, Edinburgh Napier University, Sighthill Campus, Edinburgh, EH11 4BN, United Kingdom.
authors.forename: Peter G
authors.initials: PG
authors.lastname: Barlow
authors.affiliation: Moredun Research Institute, Pentlands Science Park, Edinburgh, Midlothian, EH26 0PZ, United Kingdom.
authors.forename: Nick
authors.initials: N
authors.lastname: Wheelhouse
mesh_terms: D002460:Cell Line; D002695:Chlamydiales / Q000378:metabolism*; D004847:Epithelial Cells / Q000378:metabolism*; D057809:HEK293 Cells; D006801:Humans; D007113:Immunity, Innate / Q000502:physiology; D016209:Interleukin-8 / Q000378:metabolism*; D020928:Mitogen-Activated Protein Kinases / Q000378:metabolism*; D051192:Receptors, Pattern Recognition / Q000378:metabolism
chemical_list: C508606:CXCL8 protein, human; D016209:Interleukin-8; D051192:Receptors, Pattern Recognition; D020928:Mitogen-Activated Protein Kinases