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X. Huang, W. Du, S. A. McClellan, L. D. Hazlett; IL-33 Contributes to Host Resistance Against Pseudomonas Aeruginosa Keratitis by Promoting a Th2 Immune Response. Invest. Ophthalmol. Vis. Sci. 2008;49(13):2823. doi: https://doi.org/.
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© ARVO (1962-2015); The Authors (2016-present)
To elucidate the role of IL-33, a specific ligand of the IL-1/TLR receptor family member ST2, in resistance to Pseudomonas aeruginosa (P. aeruginosa) keratitis.
IL-33 mRNA expression was tested using real-time RT-PCR in C57BL/6 (B6) vs. BALB/c mice before and after P. aeruginosa (1x106 CFU/µl, ATCC strain 19660) challenge. Infected B6 mice also were tested after subconjunctival injection with recombinant mouse IL-33 (rmIL-33) protein or PBS. Corneal disease progress was monitored by clinical score and cytokines/chemokines were tested by real-time PCR and ELISA assays. To further investigate IL-33 regulation of corneal inflammation, an in vitro study was performed using RAW264.7 macrophage-like cells in which ST2 was overexpressed and stimulation of these cells with recombinant mouse IL-33. Cytokine/chemokine expression in rmIL-33 vs. PBS treated cells was measured by real-time PCR and/or ELISA.
IL-33 mRNA was constitutively expressed in the uninfected, normal cornea of both mouse groups. IL-33 mRNA levels in the cornea of BALB/c vs. B6 mice were elevated significantly at 1-5 days p.i., and peaked at 3 days p.i. B6 mice treated with rmIL-33 compared with PBS controls showed decreased corneal opacity and less perforation (at 5 days p.i.). These mice also exhibited lower corneal mRNA levels for IL-1β, MIP-2 and TNF-α. In contrast, production of an anti-inflammatory cytokine (TGF-β) and Th2-type cytokines (IL-4, -5 and -10) were significantly upregulated. Protein levels for TNF-α and IL-10 were selectively confirmed by ELISA in the cornea of rmIL-33 vs. PBS treated mice. In vitro, RAW264.7 cells transiently transfected with ST2 and stimulated with rmIL-33 vs. PBS also showed significantly increased Th2-type cytokines, but markedly decreased Th1-type cytokine (IFN-γ) as well as IL-1β and MIP-2 production.
IL-33 participates in resistance to P. aeruginosa keratitis by negatively regulating corneal inflammation through promotion of a Th2-type immune response and up-regulation of anti-inflammatory cytokine (TGF-β) production.
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