title: Synergistic induction of eotaxin and VCAM-1 expression in human corneal fibroblasts by staphylococcal peptidoglycan and either IL-4 or IL-13.
abstract: BACKGROUND
  Common features of allergic or atopic ocular and skin diseases are the participation of Th2 lymphocytes and eosinophils and colonization by Staphylococcus aureus. To examine the role of interaction between Th2 cells and bacterial infection in tissue eosinophilia, we determined the effects of Th2 cytokines and peptidoglycan derived from the cell wall of S. aureus on corneal fibroblasts.
  
  
  METHODS
  Chemokine concentrations and the cell surface expression of adhesion molecules were determined by ELISAs, and chemokine and adhesion molecule mRNAs were quantitated by real-time PCR analysis. Signaling by the transcription factor NF-κB was evaluated by immunoblot and immunofluorescence analyses as well as by assay of DNA binding activity.
  
  
  RESULTS
  Among Th2 cytokines tested, only interleukin (IL)-4 and IL-13 induced a low level of eotaxin release by corneal fibroblasts, as did peptidoglycan. However, the combination of peptidoglycan and either IL-4 or IL-13 induced a marked synergistic increase both in eotaxin release (without affecting that of IL-8) and in the abundance of eotaxin mRNA. The combination of peptidoglycan and IL-4 or IL-13 also synergistically increased the surface expression of VCAM-1, but not that of ICAM-1. Peptidoglycan activated NF-κB in corneal fibroblasts, and inhibitors of NF-κB attenuated eotaxin release induced by peptidoglycan alone or in combination with IL-4 or IL-13.
  
  
  CONCLUSIONS
  Interaction of innate and adaptive immunity, as manifested by synergistic stimulation of eotaxin and VCAM-1 expression in corneal fibroblasts by peptidoglycan and Th2 cytokines, may play an important role in tissue eosinophilia associated with ocular allergy.
authors.affiliation: Department of Ophthalmology and Visual Science, Kochi Medical School, Japan. k.fukuda@kochi−u.ac.jp
authors.forename: Ken
authors.initials: K
authors.lastname: Fukuda
authors.forename: Teruo
authors.initials: T
authors.lastname: Nishida
authors.forename: Atsuki
authors.initials: A
authors.lastname: Fukushima
mesh_terms: D002478:Cells, Cultured; D019742:Chemokines, CC / Q000235:genetics* / Q000378:metabolism; D060527:Corneal Keratocytes / Q000187:drug effects / Q000378:metabolism*; D004357:Drug Synergism; D004789:Enzyme Activation / Q000187:drug effects; D005786:Gene Expression Regulation / Q000187:drug effects; D006801:Humans; D007155:Immunologic Factors / Q000494:pharmacology; D018793:Interleukin-13 / Q000494:pharmacology*; D015847:Interleukin-4 / Q000494:pharmacology*; D016328:NF-kappa B / Q000378:metabolism; D010457:Peptidoglycan / Q000276:immunology / Q000494:pharmacology*; D012333:RNA, Messenger / Q000235:genetics; D013211:Staphylococcus aureus / Q000276:immunology*; D019010:Vascular Cell Adhesion Molecule-1 / Q000235:genetics* / Q000378:metabolism
chemical_list: D019742:Chemokines, CC; D007155:Immunologic Factors; D018793:Interleukin-13; D016328:NF-kappa B; D010457:Peptidoglycan; D012333:RNA, Messenger; D019010:Vascular Cell Adhesion Molecule-1; D015847:Interleukin-4