Decreased PPAR-γ expression in the conjunctiva and increased expression of TNF-α and IL-1β in the conjunctiva and tear fluid of dry eye mice

Mol Med Rep. 2014 May;9(5):2015-23. doi: 10.3892/mmr.2014.2041. Epub 2014 Mar 12.

Abstract

The aim of this study was to investigate the expression of peroxisome proliferator-activated receptor γ (PPAR-γ), tumor necrosis factor (TNF)-α and interleukin (IL)-1β in the conjunctiva and the association between inflammatory cytokines and PPAR-γ in dry eye mice. Dry eye was induced in 6-week-old female C57 mice. mRNA expression of PPAR-γ, TNF-α and IL-1β were measured. PPAR-γ protein expression in the conjunctiva, and the contents of TNF-α and IL-1β in the conjunctiva and tear-wash fluid were determined. A PPAR-γ agonist, pioglitazone (PIO), was used to treat dry eye mice. Dry eye mice presented with similar manifestations as in humans. The PPAR-γ expression in the conjunctiva of dry eye mice was downregulated, accompanied by increased contents of TNF-α and IL-1β. PIO treatment markedly reduced the contents of TNF-α and IL-1β in tear fluid of dry eye mice. Following PIO treatment, the PPAR-γ expression increased markedly. PIO may activate PPAR-γ to inhibit the expression of the inflammatory cytokines TNF-α and IL-1β in dry eye mice. This suppresses the inflammatory progression, increases the tear fluid production, elevates the tear film stability and reduces the damage to the ocular surface, exerting a therapeutic effect on dry eye.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Cell Count
  • Conjunctiva / metabolism*
  • Conjunctiva / pathology
  • Disease Models, Animal
  • Dry Eye Syndromes / drug therapy
  • Dry Eye Syndromes / genetics*
  • Dry Eye Syndromes / metabolism*
  • Dry Eye Syndromes / pathology
  • Female
  • Gene Expression Regulation
  • Goblet Cells / metabolism
  • Interleukin-1beta / genetics*
  • Interleukin-1beta / metabolism
  • Mice
  • PPAR gamma / genetics*
  • PPAR gamma / metabolism
  • Pioglitazone
  • Tears / metabolism*
  • Thiazolidinediones / administration & dosage
  • Thiazolidinediones / pharmacology
  • Time Factors
  • Tumor Necrosis Factor-alpha / genetics*
  • Tumor Necrosis Factor-alpha / metabolism

Substances

  • Interleukin-1beta
  • PPAR gamma
  • Thiazolidinediones
  • Tumor Necrosis Factor-alpha
  • Pioglitazone