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Tohru Sakimoto, Ai Yamada, Mitsuru Sawa; Release of Soluble Tumor Necrosis Factor Receptor 1 from Corneal Epithelium by TNF-α–Converting Enzyme-Dependent Ectodomain Shedding. Invest. Ophthalmol. Vis. Sci. 2009;50(10):4618-4621. doi: 10.1167/iovs.08-2669.
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purpose. An involvement of tumor necrosis factor-α–converting enzyme (TACE)–dependent ectodomain shedding in the release of soluble tumor necrosis factor receptor 1 (sTNFR1) from corneal epithelium was evaluated.
methods. In vitro experiments were performed using the human SV40-transformed human corneal epithelial cell (HCEC) line. Ectodomain shedding was stimulated by phorbol myristate acetate (PMA, 3 μM) or peptidoglycan (PGN, 100 μg/mL), with or without TACE inhibition, using TNF-α processing inhibitor-1 (TAPI-1, 250 μg/mL) or tissue inhibitor of metalloproteinase-3 (TIMP-3, 2 μg/mL) by addition to the HCEC culture medium. The concentrations of sTNFR1 in culture medium were analyzed by enzyme-linked immunosorbent assay. To induce an inflammatory response in the ocular surface, corneal alkali burn of BALB/c mice was made from a filter paper dipped in 1 N NaOH solution. TNFR1 expression in corneal and conjunctival epithelia was evaluated by immunohistochemistry 28 days after wounding.
results. In HCEC culture medium, sTNFR1 release was significantly increased by the addition of PMA (t-test, P < 0.01) or PGN (P < 0.01). The increased release of sTNFR1 was significantly inhibited by the addition of TAPI-1 or TIMP-3, indicating the possibility of TACE-dependent ectodomain shedding of TNFR1. In the corneal alkali burn model, TNFR1 was expressed in corneal and conjunctival epithelia.
conclusions. TACE-dependent ectodomain shedding of sTNFR1 was recognized in corneal epithelium. In the inflamed ocular surface, TNFR1 was expressed in the corneal and conjunctival epithelia after alkali burn treatment. sTNFR1, released from the ocular surface, may play an anti-inflammatory role in the inflammatory condition.
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