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Satoshi Sugaya, Tohru Sakimoto, Ai Yamada, Takako Ohnishi, Akiko Ishimori, Mitsuru Sawa; The effects of IL-6 receptor blockade on gene expressions in experimental corneal alkali burn. Invest. Ophthalmol. Vis. Sci. 2013;54(15):3883.
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Using experimental corneal alkali burn model, we previously reported the suppressive effect of topical instillation of anti-Interleukin-6 receptor (IL-6R) antibody on infiltrations of inflammatory cells. Using this model, we investigated the gene expressions of inflammation-related factors and chemotactic factors.
Unilateral eye of corneal alkali burn was made using a filter paper dipped in 1 N NaOH solution using BALB/c mice. Three eyes of 3 mice were treated by topical instillation of anti-IL-6R antibody solution (MR16-1, 2 µg/µL) from day 5 to day 28 after wounding. (MR16-1 group)(from day 5 to day 14; 3 times/day, from day 15 to day 28; 2 times/day) The control group (3 eyes of 3 mice, PBS group) underwent topical 0.01M PBS (pH 7.4) solution. The mice were euthanatized on day 28 and 2-μm-thick sections were made. Corneal stroma section was made using laser capture microdissection system, and total RNA in the specimens was determined by quantitative PCR array method (Mouse Th17 Response Array, QIAGEN).
In MR16-1 group, MMP (matrix metalloproteinase)-13 (6.39±3.54; mean ± SD) expression was decreased by six times compared with that in PBS group. The chemotactic factors of macrophage, MCP (monocyte chemotactic protein)-1 (5.83±1.95) and CCL22 (2.78±0.43), were decreased in MR16-1 group compared with those in PBS group. In MR16-1 group, IL-17RE, the receptor for IL-17, was higher two times values than that in PBS group (2.37±0.15).
Anti-inflammatory effect of topical instillation of anti-IL-6R antibody could be caused by the suppression of chemokines and MMP. Because IL-17 producing cells are induced by IL-6 signaling, the up-regulation of IL-17R by IL-6R blockade may have the relationship with IL-6R signal transduction.
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