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D. Miyazaki, C. Huang, D.S. Friend, R.L. Stevens, S.J. Ono; Essential Role of IL-6 in Mouse Mast Cell Protease-7-mediated Eosinophilia and Neutrophilia in the Ocular Surface : Implication for Allergic Conjunctivitis . Invest. Ophthalmol. Vis. Sci. 2003;44(13):3751.
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© ARVO (1962-2015); The Authors (2016-present)
Purpose: Mast cells release large amount of tryptase during allergic inflammation. Murine mast cell protease-7 (mMCP-7) is a murine homologue of tryptase and is abundantly expressed on the ocular surface. However, its roles remain obscure. This study was conducted to analyze mMCP-7-mediated pathology in the ocular surface and to reveal its molecular mechanism. Methods: To understand roles of mMCP-7 in ocular allergy, mMCP-7 deficient C57BL/6 or control strains (A/J or SWR/J) were immunized and challenged for allergen-induced hypersensitivity reactions (Fel d1 or short ragweed was used for allergen sensitization). Pathological effects induced by mMCP-7 was evaluated by injecting recombinant mMCP-7 or pro-enzyme into the ocular surface of naive mice. The ocular surface tissue samples were analyzed by histological examination. To reveal molecular mechanism of mMCP-7-mediated effector activation, RNA analysis using RT-PCR or RNase protection assay was performed on mMCP-7-treated ocular tissue. Results: On allergen (Fel d1) challenge, sensitized-C57BL/6 (mMCP-7(-/-)) showed impaired hypersensitivity reactions (early phase and late phase) compared to mMCP-7 (+/+) strains (A/J or SWR/J). This was independent of allergen used. Thus, an important role for mMCP-7 in allergic hypersensitivity-mediated pathological responses was suggested. Subconjunctivally injected-mMCP-7, but not pro-enzyme, induced recruitment of eosinophils and neutrophils into the ocular surface of naive mice. Since no significant difference of responsiveness was observed between mMCP-7 (+/+) and (-/-) strains, mMCP-7 responsiveness was independent of intrinsic mMCP-7. RNA analysis of mMCP-7-treated ocular tissue showed an induction of IL-6 mRNA, followed by MCP-1, MIP-2, MIP-1ß, and lymphotactin mRNAs. This suggested an involvement of IL-6 in mMCP-7-mediated-effector activation. The mMCP-7-induced inflammatory cell recruitment was abolished in IL-6 deficient C57BL/6. Together, we conclude that IL-6 is critical for mMCP-7-mediated effector activation. Conclusions: mMCP-7 induces eosinophilia and neutrophilia on the ocular surface via activation of IL-6.
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