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K. Fukuda, Y. Nakamura, A. Fukushima, T. Sumi, H. Ueno, N. Kumagai, T. Nishida; Interaction With Eosinophils Promotes Extracellular Matrix and Chemokine Synthesis by Conjunctival Fibroblasts. Invest. Ophthalmol. Vis. Sci. 2007;48(13):5175.
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Fibroproliferative lesions known as giant papillae are a characteristic of vernal keratoconjunctivitis. The numbers of inflammatory cells (including eosinophils) and of resident fibroblasts as well as the amount of extracellular matrix (ECM) are increased in giant papillae compared with those in the surrounding normal tissue. We examined the potential role of eosinophil-fibroblast interaction in the development of giant papillae by determining the effects of eosinophils on the production of ECM and chemokines by conjunctival fibroblasts.
Human conjunctival fibroblasts were cultured with human eosinophils or eosinophil conditioned medium (CM). The amounts of procollagen type I C-peptide and fibronectin released into culture medium were determined with the use of enzyme immunoassays. The concentrations of chemokines and the phosphorylation of signal transduction proteins were evaluated with the use of multiplex bead arrays.
Coculture with eosinophils or culture with eosinophil CM stimulated the release of procollagen type I C-peptide and fibronectin as well as that of the chemokines eotaxin, monocyte chemoattractant protein-1, and interleukin-8 from conjunctival fibroblasts. Eosinophil CM also induced the phosphorylation of ERK, p38, and IΚB in conjunctival fibroblasts, and the release of chemokines by eosinophil CM-stimulated fibroblasts was blocked by inhibitors of the corresponding signaling pathways.
These results indicate that factors released by eosinophils increase the synthesis of ECM and chemokines by conjunctival fibroblasts, suggesting that eosinophil-fibroblast interaction contributes to the excessive deposition of ECM and amplification of allergic inflammation associated with giant papillae.
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