Effects of Th2 cytokines on expression of collagen, MMP-1, and TIMP-1 in conjunctival fibroblasts

Invest Ophthalmol Vis Sci. 2003 Jan;44(1):183-9. doi: 10.1167/iovs.02-0420.

Abstract

Purpose: 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.

MeSH terms

  • Cell Division
  • Cells, Cultured
  • Collagen / biosynthesis*
  • Collagen / genetics
  • Conjunctiva / cytology
  • Conjunctiva / drug effects*
  • Conjunctiva / metabolism
  • Conjunctivitis, Allergic / pathology
  • Cytokines / pharmacology*
  • Fibroblasts / drug effects
  • Fibroblasts / metabolism
  • Humans
  • Matrix Metalloproteinase 1 / biosynthesis*
  • Matrix Metalloproteinase 1 / genetics
  • RNA, Messenger / metabolism
  • Recombinant Proteins
  • Reverse Transcriptase Polymerase Chain Reaction
  • Th2 Cells / chemistry*
  • Tissue Inhibitor of Metalloproteinase-1 / biosynthesis*
  • Tissue Inhibitor of Metalloproteinase-1 / genetics

Substances

  • Cytokines
  • RNA, Messenger
  • Recombinant Proteins
  • Tissue Inhibitor of Metalloproteinase-1
  • Collagen
  • Matrix Metalloproteinase 1