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D.-Q. Li, F. Bian, S. Chotikavanich, S. C. Pflugfelder; Thymic Stromal Lymphopoietin, a Novel Cytokine Linking Local Inflammation to Innate and Adaptive Immune Response in the Human Ocular Surface. Invest. Ophthalmol. Vis. Sci. 2008;49(13):3720. doi: https://doi.org/.
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Thymic stromal lymphopoietin (TSLP) is a recently identified epithelial cell-derived cytokine that strongly activates dendritic cells and can initiate allergic and inflammatory diseases. This study was to investigate the expression and regulation of TSLP and its possible role in ocular surface diseases.
Primary human corneal epithelial cells and conjunctival fibroblasts were established from limbal and conjunctival explants obtained from normal donors and pterygium patients respectively. The cultures were treated with TNF-α, IL-1β, IL-4, IL-13 or their combinations for 4 and 24 hrs. TSLP mRNA expression was determined by real time PCR with TaqMan primers and probes, and its protein levels were measured by ELISA. NF-kB activation was detected by immunostaining and cell-based activation ELISA. Human conjunctival epithelial specimens were collected by impression cytology from 4 normal and 4 dry eye subjects.
TSLP was expressed by primary cultured human corneal epithelial cells and conjunctival fibroblasts. Exogenously added proinflammatory cytokines (IL-1β and TNF-α) and Th2 cytokines (IL-13 and IL-4) induced the TSLP mRNA levels by 2-4 or 6-9 folds respectively, while TNF-α synergized with IL-13 or IL-4 to promote TSLP expression to 16-23 fold in corneal epithelial cells. TNF-α induced NF-kB p65 protein nuclear translocation and p65 Ser536 phosphorylation. NF-kB activation inhibitor (quinazoline) and IKK inhibitor II (Wedelolactone) blocked the NF-kB p65 nuclear translocation and phosphorylation, and also suppressed TSLP expression induced by TNF-α. In cultured normal conjunctival fibroblasts, the TSLP transcripts were dramatically stimulated 3-8 fold by IL-1β and TNF-α, but not by IL-4 and IL-13. Interestingly, the mRNA levels of TNF-α and TSLP were co-elevated in the conjunctival epithelial specimens from dry eye patients and in the conjunctival fibroblasts from pterygium patients.
These findings demonstrate for the first time that the human corneal epithelial cell and conjunctival fibroblast derived TSLP is induced by inflammatory and Th2 cytokines, partially through NF-kB pathway. TSLP is a novel cytokine that links local inflammation to innate and adaptive immune response, and might play a vital role in regulating immune response in ocular surface inflammatory disease. Further study is going on to evaluate the interactions between the corneal cells and dendritic cells.
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