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U. Schulze, S. Sel, N. Barker, F. Paulsen; Trefoil Factor Family Peptid 3 (TFF3) in Corneal Epithelial Cells Under Experimental Dry Eye Conditions. Invest. Ophthalmol. Vis. Sci. 2009;50(13):4273.
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The Trefoil Factor Family peptide 3 (TFF3) has protective functions but our recent results have indicated that compared to acute inflammatory conditions it seems to have opposed effects in a chronically inflamed environment. Since dry eye syndrome is characterized by hyperosmolarity of the tear fluid, increased apoptosis, extra cellular matrix (ECM) remodelling as well as chronic inflammation we studied the role of TFF3 under experimental dry eye conditions and analyzed the effect of TFF3 on matrix metalloproteinases (MMPs) and tissue inhibitors of matrix metalloproteinases (TIMPs).
Tear fluid collected from patients with dry eye syndrome was investigated using a so called ocular ferning test to study the influence of recombinant human TFF3 (rhTFF3) on pattern formation of the tear film. After treating corneal epithelial cells (Araki-Sasaki cell line, HCE) with proinflammatory cytokines (IL-1β, TNF, IFNγ), hyperosmolar media (475, 550mOsM) and UVB radiation, the expression of TFF3 was analyzed by RT-PCR and immunohistochemistry. To study the rhTFF3 effect on ECM remodelling MMP and TIMP mRNA expression levels were evaluated by real time PCR after stimulation of HCE cells with IL-1β and hyperosmolar medium (550mOsM) together with rhTFF3 (10µg/ml and 300µg/ml).
Ocular ferning test results revealed a strong positive influence of rhTFF3 on the crystalization pattern of the tear fluid from patients with dry eye syndrome whereas it had no effect on tear fluid from healthy volunteers. TFF3 expression was induced under simulated dry eye stress conditions compared to controls. rhTFF3 treatment increased IL-1β-induced MMP9 expression levels but decreased IL-1β- and hyperosmolarity-induced MMP13 expression. Stimulation of corneal epithelial cells only with rhTFF3 resulted in an upregulated MMP2 expression but had no further effect together with IL-1β. Other MMPs and TIMPs were not affected by rhTFF3 treatment.
The induction of TFF3 in a pathological environment at the ocular surface and our ocular ferning test results support the potential protective function of TFF3. rhTFF3 effects on MMP13 seem also to sustain this role. However, changes in MMP2 and MMP9 expression levels indicate different rhTFF3 consequences and need further elucidation.
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