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O. Sakai, H. Takahashi, Y. Tamada, J. Inoue, M. Azuma; Involvement of NFkB and STAT6 on Eotaxin-1, IL-8 and RANTES Production in Human Conjunctival Fibroblasts and Epithelial Cells. Invest. Ophthalmol. Vis. Sci. 2008;49(13):430.
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© ARVO (1962-2015); The Authors (2016-present)
Accumulation of inflammatory cells in conjunctiva of chronic allergic conjunctivitis is caused by chemokines. It has been reported that NFkB and STAT6 are implicated in chemokine release. In present study, we researched the modulation of NFkB and STAT6 pathway on the production of chemokines from human conjunctival fibroblasts and epithelial cells.
Cultured human conjunctival fibroblasts and epithelial cells were incubated with TNF-α, IL-4 or combination of TNF-α and IL-4 (TNF-α + IL-4) For the inhibition study, the cells were preexposed to IKK inhibitor BMS-345541 or JAK inhibitor 1 for 30 min, then treated with TNF-α + IL-4. The concentrations of eotaxin-1, IL-8 and RANTES in the culture supernatant were subsequently measured by ELISA assay. The activation of NFkB and STAT6 were evaluated by immunoblots of IkB-α and phosphorylation of STAT6.
IL-8 and RANTES were produced by TNF-α and TNF-α + IL-4 from both of human conjunctival fibroblasts and epithelial cells. On the other hand, eotaxin-1 was produced by TNF-α + IL-4 from only conjunctival fibroblasts. Also, IkB-α was degraded by TNF-α and TNF-α + IL-4. Phosphorylation of STAT6 was induced by IL-4 and TNF-α + IL-4. In addition, BMS-345541 significantly inhibited all chemokines production and IkB-α degradation in both of conjunctival fibroblasts and epithelial cells. JAK inhibitor 1 also inhibited eotaxin-1 production and phosphorylation of STAT6 in conjunctival fibroblasts.
We found that the production of eotaxin-1 from conjunctival fibroblast was regulated by NFkB and STAT6, and the production of IL-8 and RANTES from conjunctival fibroblasts and epithelial cells was regulated by NFkB.
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