Flagellin suppresses the inflammatory response and enhances bacterial clearance in a murine model of Pseudomonas aeruginosa keratitis.

Flagellin suppresses the inflammatory response and enhances bacterial clearance in a murine model of Pseudomonas aeruginosa keratitis. Research Abstract Details 

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Flagellin suppresses the inflammatory response and enhances bacterial clearance in a murine model of Pseudomonas aeruginosa keratitis. Abstract Text:

Ashok Kumar,Linda D Hazlett,Fu-Shin X Yu,Ashok Kumar,Linda D Hazlett,Fu-Shin X Yu,Ashok Kumar,Linda D Hazlett,Fu-Shin X Yu,

Pseudomonas aeruginosa is a common organism associated with bacterial keratitis, especially in extended-wear contact lens users. In the present study, we determined that pretreatment of cultured human corneal epithelial cells with flagellin isolated from the P. aeruginosa PAO1 strain attenuated cytokine production when the cells were challenged with a cytotoxic strain (ATCC 19660), suggesting a potential use of bacterial flagellin to downregulate infection-associated inflammation in vivo. Administration of flagellin via the subconjunctival and intraperitoneal routes 24 h prior to Pseudomonas inoculation significantly improved the disease outcome, preserved structural integrity and transparency, and thus maintained vision in otherwise perforated corneas of C57BL/6 (B6) mice. The flagellin pretreatment resulted in suppression of polymorphonuclear leukocyte infiltration at a late stage of infection but not at an early stage of infection, decreased the expression of proinflammatory cytokine genes (genes encoding interleukin-1beta [IL-1beta], macrophage inflammatory protein 2, IL-12, and gamma interferon), and greatly enhanced bacterial clearance in the corneas of B6 mice probably through induced expression of the cathelicidin-related antimicrobial peptide and inducible nitric oxide synthase. This is the first report that describes the protective mechanisms induced by a Toll-like receptor agonist that not only curbs the host inflammatory response but also eliminates invading bacteria in the B6 mouse cornea.

Flagellin suppresses the inflammatory response and enhances bacterial clearance in a murine model of Pseudomonas aeruginosa keratitis. Publishing Authors By Initials

A Kumar,LD Hazlett,FS Yu,A Kumar,LD Hazlett,FS Yu,A Kumar,LD Hazlett,FS Yu,

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Flagellin suppresses the inflammatory response and enhances bacterial clearance in a murine model of Pseudomonas aeruginosa keratitis. Journal Published:

PUBLICATION TYPE: Research Support, Non-U.S. Gov

Journal: Infection and immunity

VOLUME: 76

Page Numbers: 89-96

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ISSN: 1098-5522

DAY: 15

MONTH: 10

YEAR: 2007

Flagellin suppresses the inflammatory response and enhances bacterial clearance in a murine model of Pseudomonas aeruginosa keratitis. Information

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LANGUAGE: eng

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Grant and Affiliation Information for Flagellin suppresses the inflammatory response and enhances bacterial clearance in a murine model of Pseudomonas aeruginosa keratitis.

AFFILIATION: Kresge Eye Institute/Department of Ophthalmo, Wayne State University School of Medicine, Detroit, MI 48201, USA.

Country: United States

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MEDLINETA: Infect Immun

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