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T. Sakimoto, A. Yamada, J. Shoji, M. Sawa; TACE(ADAM17) Dependent Shedding of Soluble TNF Receptor in Conjunctival Epithelium. Invest. Ophthalmol. Vis. Sci. 2008;49(13):2393.
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© ARVO (1962-2015); The Authors (2016-present)
To evaluate the involvement of tumor necrosis factor-alpha converting enzyme (TACE, ADAM17) in ectodomain shedding of TNF receptor in conjunctival epithelium.
The corneal alkali burn of BALB/c mice was made using a filter paper dipped in 1N NaOH solution. TNF receptor 1 (TNFR1) expression in conjunctiva was evaluated by immunohistochemistry with time course (3eyes each). In vitro experiments were performed using human conjunctival epithelial cell (HCjEC) line. Peptidoglycan (PGN, 100µg/mL, 24hours) alone or PGN and TACE inhibitor (TAPI-1, 250µg/mL, 4hours) were added to HCjEC medium. s (soluble) TNFR1 concentration in supernatant of the culture medium was analyzed by ELISA.
In corneal alkali burn model, TNFR1 was expressed in conjunctival epithelium 14 days after the alkali burn. In HCjEC cultured medium, sTNFR1 release was significantly increased by adding of PGN (t-test, p<0.05). This increased release of sTNFR1 was significantly inhibited by TAPI-1 (t-test, p<0.05), indicating the participation of TACE in this sTNFR1 releasing process.
In conjunctiva, TNFR1 was expressed in the epithelium after the corneal alkali burn and TACE dependent shedding of sTNFR1 was recognized in conjunctival epithelium. sTNFR1, released from ocular surface, might play anti-inflammatory role in inflammatory condition by neutralizing TNF-α.
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