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Invest Ophthalmol Vis Sci. 2010 Mar;51(3):1524-32. doi: 10.1167/iovs.09-3983. Epub 2009 Nov 5.

IL-33 shifts macrophage polarization, promoting resistance against Pseudomonas aeruginosa keratitis.

Author information

  • 1Department of Anatomy and Cell Biology, Wayne State University School of Medicine, Detroit, Michigan 48201, USA. lhazlett@med.wayne.edu

Abstract

PURPOSE:

To determine the role of IL-33 in resistance to Pseudomonas aeruginosa keratitis.

METHODS:

Corneal IL-33 mRNA and protein levels were tested in susceptible C57BL/6 (B6) and resistant BALB/c mice. B6 mice were injected with recombinant mouse IL-33 (rmIL-33) and disease severity, bacterial load, polymorphonuclear neutrophils (PMN) infiltrate, gene expression of inflammatory, and T-helper (Th)1/Th2 cytokines were tested by RT-PCR. IL-33 signaling and macrophage (Mvarphi) polarization also were examined.

RESULTS:

IL-33 mRNA and protein were expressed constitutively in the normal corneas of both groups and were significantly elevated at 1 to 5 days after infection in BALB/c over B6 mice. rmIL-33-treated B6 mice showed less severe disease than did PBS controls and exhibited decreased bacterial load, PMN infiltrate, and corneal mRNA levels for IL-1beta, MIP-2, and TNF-alpha. Th2-type cytokines (IL-4, -5, -10) also were significantly upregulated, and protein levels for TNF-alpha and IL-10 confirmed the mRNA data. To further investigate IL-33 in corneal inflammation, it was overexpressed in Mvarphi (RAW264.7 cells). This significantly increased IL-5 and IL-10, while it decreased IFN-gamma and other pro-inflammatory cytokines. The role of the Mvarphi was further tested in infected rmIL-33 compared with PBS-injected mice. Immunostaining showed that rmIL-33 injection shifted Mvarphi polarization from NO synthase 2 to arginase production. Furthermore, peritoneally elicited cells (B6 mice) treated with lipopolysaccharide and rmIL-33 exhibited elevated ST2 levels and a shift from IL-12 to IL-10 mRNA production.

CONCLUSIONS:

These data provide evidence that IL-33 promotes a Th2-type immune response and reduces inflammation by polarizing the Mvarphi production of anti-inflammatory mediators in the cornea.

PMID:
19892870
PMCID:
PMC2868421
DOI:
10.1167/iovs.09-3983
[PubMed - indexed for MEDLINE]
Free PMC Article
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