title: Effects of Th2 cytokines on expression of collagen, MMP-1, and TIMP-1 in conjunctival fibroblasts.
abstract: OBJECTIVE
  To determine whether cytokines involved in chronic allergic conjunctival disorders may affect formation of giant papillae and tissue remodeling.
  
  
  METHODS
  Conjunctival fibroblast cultures were challenged with different concentrations of human recombinant interleukin (IL)-4, IL-13, interferon (IFN)-gamma and tumor necrosis factor (TNF)-alpha. Procollagens I (PIP) and III (PIIIP), matrix metalloproteinase (MMP)-1 and -9, and tissue inhibitor of metalloproteinase (TIMP)-1 were measured in supernatants, and their respective mRNAs were evaluated by RT-PCR.
  
  
  RESULTS
  IL-4 and -13 (10 ng/mL) significantly increased production and expression of PIP compared with nonstimulated cells, whereas IFN-gamma elicited the opposite effect, at both the protein and mRNA levels. Both IL-4 and -13 significantly decreased production of MMP-1 and increased that of TIMP-1, whereas TNF-alpha increased production of MMP-1 and -9. Expression of MMP-1 was reduced by IL-4 and increased by the other tested cytokines, whereas expression of TIMP-1 was increased by all tested cytokines.
  
  
  CONCLUSIONS
  IL-4 and -13 increased production of collagen and modified the equilibrium between MMP-1 and its inhibitor, TIMP-1. These effects were partially opposed by IFN-gamma and TNF-alpha.
authors.affiliation: Department of Neuroscience, Ophthalmology and Ocular Inflammation Unit, University of Padua, via Foscari 8, 35127 Padua, Italy. mdvol@tin.it
authors.forename: Andrea
authors.initials: A
authors.lastname: Leonardi
authors.forename: Roberta
authors.initials: R
authors.lastname: Cortivo
authors.forename: Iva
authors.initials: I
authors.lastname: Fregona
authors.forename: Mario
authors.initials: M
authors.lastname: Plebani
authors.forename: Antonio G
authors.initials: AG
authors.lastname: Secchi
authors.forename: Giovanni
authors.initials: G
authors.lastname: Abatangelo
mesh_terms: D002455:Cell Division; D002478:Cells, Cultured; D003094:Collagen / Q000096:biosynthesis* / Q000235:genetics; D003228:Conjunctiva / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D003233:Conjunctivitis, Allergic / Q000473:pathology; D016207:Cytokines / Q000494:pharmacology*; D005347:Fibroblasts / Q000187:drug effects / Q000378:metabolism; D006801:Humans; D020781:Matrix Metalloproteinase 1 / Q000096:biosynthesis* / Q000235:genetics; D012333:RNA, Messenger / Q000378:metabolism; D011994:Recombinant Proteins; D020133:Reverse Transcriptase Polymerase Chain Reaction; D018418:Th2 Cells / Q000737:chemistry*; D019715:Tissue Inhibitor of Metalloproteinase-1 / Q000096:biosynthesis* / Q000235:genetics
chemical_list: D016207:Cytokines; D012333:RNA, Messenger; D011994:Recombinant Proteins; D019715:Tissue Inhibitor of Metalloproteinase-1; D003094:Collagen; D020781:Matrix Metalloproteinase 1