title: Corneal and conjunctival fibroblasts are major sources of eosinophil-recruiting chemokines.
abstract: BACKGROUND
  Differential expression of chemokine genes were investigated in various types of ocular surface cells.
  
  
  METHODS
  Primary cultures of human corneal epithelial cells (n = 3), corneal fibroblasts (n = 2), conjunctival epithelial cells (n = 2) and conjunctival fibroblasts (n = 2) were established and incubated with or without interleukin (IL)-4 (30ng/ml) and tumor necrosis factor (TNF)-alpha(30ng/ml) for 24 hours. Gene transcription levels of 33 chemokines and production of 4 chemokines were analyzed.
  
  
  RESULTS
  After stimulation, chemokine expression increased for 18 of 33 coded chemokine gene transcripts. In stimulated conjunctival and corneal cells, CC chemokine genes increased in fibroblasts (expression of 6 out of 8 genes), while CXC chemokine genes increased in both epithelial cells (expression of 4 out of 9 genes in conjunctival epithelial cells and 7 out of 9 genes in corneal epithelial cells) and in fibroblasts (expression of 8 out of 9 genes in conjunctival and corneal fibroblasts). Except for MCP-1, gene transcription levels for most CC chemokines were inducible and, except for IP-10 and I-TAC, most CXC chemokines were constitutively expressed. Corneal epithelial cell and fibroblast production patterns for eotaxin-1, MCP-1 and IP-10 were comparable to the mRNA expression pattern.
  
  
  CONCLUSIONS
  Corneal and conjunctival fibroblasts exhibited marked increases in the expression of chemokines upon stimulation with TNF-alpha and IL-4, suggesting that fibroblasts may be one of the primary sources of chemokines in allergic conjunctival diseases. Therefore, regulation of chemokine production from these cells may be an effective strategy for treating such diseases.
authors.affiliation: Department of Ophthalmology, Keio University, Tokyo, Japan. BR5K-FKGW@asahi-net.or.jp
authors.forename: Kazumi
authors.initials: K
authors.lastname: Fukagawa
authors.forename: Naoko
authors.initials: N
authors.lastname: Okada
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Fujishima
authors.forename: Toshiharu
authors.initials: T
authors.lastname: Nakajima
authors.forename: Yoji
authors.initials: Y
authors.lastname: Takano
authors.forename: Mari
authors.initials: M
authors.lastname: Tanaka
authors.forename: Murat
authors.initials: M
authors.lastname: Dogru
authors.forename: Yoshiyuki
authors.initials: Y
authors.lastname: Satake
authors.forename: Kazuo
authors.initials: K
authors.lastname: Tsubota
authors.forename: Hirohisa
authors.initials: H
authors.lastname: Saito
mesh_terms: D018929:Cell Culture Techniques; D002478:Cells, Cultured; D018925:Chemokines / Q000096:biosynthesis* / Q000235:genetics; D002633:Chemotaxis / Q000235:genetics / Q000276:immunology; D003228:Conjunctiva / Q000473:pathology; D003315:Cornea / Q000473:pathology; D004804:Eosinophils / Q000276:immunology; D004847:Epithelial Cells / Q000276:immunology / Q000378:metabolism* / Q000473:pathology; D005347:Fibroblasts / Q000276:immunology / Q000378:metabolism* / Q000473:pathology; D020869:Gene Expression Profiling; D005786:Gene Expression Regulation; D006801:Humans; D015847:Interleukin-4 / Q000276:immunology; D020411:Oligonucleotide Array Sequence Analysis; D014409:Tumor Necrosis Factor-alpha / Q000276:immunology
chemical_list: D018925:Chemokines; D014409:Tumor Necrosis Factor-alpha; D015847:Interleukin-4