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X. Huang, W. Du, L. D. Hazlett; ST2 Is Required for Th2 Responsiveness and Resistance to Pseudomonas Aeruginosa Keratitis. Invest. Ophthalmol. Vis. Sci. 2007;48(13):727.
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© ARVO (1962-2015); The Authors (2016-present)
To elucidate the role of ST2, a member of the TLR/IL-1R (TIR) superfamily, in resistance to Pseudomonas aeruginosa (P. aeruginosa) keratitis in BALB/c mice.
ST2 mRNA and protein levels were tested using real-time PCR and western-blot in C57BL/6 (B6, susceptible) vs. BALB/c (resistant) mice before and after P. aeruginosa (5 µl of 106 CFU/µl, ATCC strain 19660) challenge. Infected BALB/c mice also were tested after subconjunctival injection with rmST2/Fc fusion protein or PBS. Disease was monitored by PCR, clinical score, slit lamp, bacterial plate count, myeloperoxidase (MPO) assay to measure PMN infiltrate, and ELISA assays.
ST2 mRNA and protein were constitutively expressed in the uninfected, normal cornea of both mouse groups. ST2 levels in the cornea of BALB/c over B6 mice were elevated significantly at 1-3 days p.i., peaked at 3 and decreased at 5 days p.i. BALB/c mice treated with rmST2/Fc (a decoy to block ST2 signaling) over PBS controls showed increased corneal opacity and perforation (at 5 days p.i.). These mice also exhibited increased bacterial load, PMN infiltrate and higher corneal mRNA levels for IL-1ß, MIP-2, IL-1R1 and the Th1 type cytokine, IFN-γ. Protein levels for IL-1ß and MIP-2 were significantly upregulated in rmST2 over PBS controls. In contrast, Th2 cytokines IL-5 (mRNA) and IL-10 (mRNA and protein) were significantly reduced.
ST2 is critical in resistance to P. aeruginosa keratitis, functioning to reduce corneal infection and inflammation by negatively regulating proinflammatory cytokines, inhibiting type-1 immunity, and upregulating type-2 cytokine production, particularly IL-10.
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