Linda Dondero Hazlett

..In the absence of T-cell infiltration into the cornea, PMN do not persist in the stroma, and cytokines and chemokines are better balanced, resulting in decreased stromal destruction and the resistance response...

..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...

..The role of complement in phagocytosis and killing of P. aeruginosa was examined using serum from aged vs young donor mice...

..To determine the effects of blocking substance P (SP) interactions with its major receptor (NK1-R) using the antagonist spantide I in susceptible mice infected with Pseudomonas aeruginosa...

..This study determined the role of inducible nitric oxide synthase (iNOS) and nitric oxide (NO) in the resistance response of BALB/c mice to P. aeruginosa-induced keratitis...

..Overall, studies with these inbred mice provide a better understanding of the mechanisms of innate immune responsiveness and abrogation of immune privilege operative after P. aeruginosa corneal infection...

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..To elucidate the role of ST2, a member of the TLR/IL-1R (TIR) superfamily, in protecting against Pseudomonas aeruginosa keratitis in BALB/c mice...

..These studies of defensins in the innate immune system have implications for the prevention and treatment of a variety of infectious diseases, including bacterial ocular disease...

..Future studies will be aimed at better defining the role of Toll receptors, neuropeptides (as unconventional modulators of the immune response) and exploitation of disease control by new techniques, such as RNA silencing...

..Therefore, the purpose of this study was to test whether BALB/c mice are capable of responding to exogenous IL-12 administration, and whether disease responsiveness following P. aeruginosa challenge is modified...

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

..K) response development were evaluated for their response to infection with Pseudomonas aeruginosa. This study addresses the question of whether Th1 versus Th2 response propensity affects the pathogenesis of bacterial keratitis in mice...

..These results support a critical role for B7/CD28 costimulation in susceptibility to P. aeruginosa ocular infection...

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..HSK is more frequent and severe in BALB/c than C57BL/6 mice, and varies in severity with the strain and dose of HSV-1 used to infect the cornea...

..Despite its potential importance, the role of IL-12 in ocular infection with P. aeruginosa remains unexplored and was the purpose of this study...

..CONCLUSION: IFN-gamma regulates NO levels, and synergistic interaction between the two regulates disease outcome in resistant mice...

..The purpose of this study was to determine the role of matrix metalloproteinases (MMP) in Pseudomonas aeruginosa keratitis...

..This study tested the effect of SP injection on the resistance response (cornea heals) of BALB/c mice...

..The role of the Fas pathway was tested in Pseudomonas aeruginosa-infected mouse cornea by contrasting the responses of FasL(-/-) and wild-type (WT) mice...

..Apoptosis was examined after Pseudomonas aeruginosa corneal infection in C57BL/6 (B6, susceptible) and BALB/c (resistant) mice...

..These data provide evidence that macrophages control resistance to P. aeruginosa corneal infection through regulation of PMN number, bacterial killing and balancing pro- and anti-inflammatory cytokine levels...

..aeruginosa...

..The rat model should be valuable to delineate further the effects of contact lens wear, including the testing of additional contact lens-related complications...

..The data suggest a unique link between the nervous system and development of innate immunity in the cornea...

..These data provide evidence that IL-18 contributes to the resistance response by induction of IFN-gamma and that IFN-gamma is required for bacterial killing...

..This study used a rat contact lens (CL) model to test if high- versus low-Dk lens wear caused changes in (1) conjunctival Langerhans cell (LC) number or location; (2) Bcl-2 expression; and (3) infection risk...

..Collectively, the data provide evidence that mBD2 and mBD3 together promote resistance against corneal infection...

..aeruginosa strain. CONCLUSIONS: Downregulation of IL-1beta by ICE together with ciprofloxacin to kill bacteria may provide alternate therapy to current treatment...

..aeruginosa challenge, determining susceptibility vs. resistance to disease, and are consistent with long-term goals of providing targets for better treatment of disease...

..Collectively, the data provide evidence that mBD2, but not mBD1, is required for host resistance against P. aeruginosa-induced corneal infection...

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..To elucidate these mechanisms, caspase-1 knockout (ICE(-/-)) mice, that do not release mature IL-1 beta after endotoxin challenge, were tested...

..These data provide evidence that neuroimmune regulation of the cytokine network and host inflammatory cells functions to promote resistance against P. aeruginosa corneal infection...

..Tbeta(4) and TGFbeta-1 increase LM-5 gamma2 chain expression by independent pathways. Suppression of TGFbeta-1 further increases LM-5 gamma2 chain expression...

..These data provide evidence that SIGIRR is critical in resistance to P. aeruginosa corneal infection by down-regulating type 1 immunity, and that it negatively regulates IL-1 and TLR4 signaling...

..To determine the role of Toll-like receptor 4 (TLR4) in Pseudomonas aeruginosa (P. aeruginosa) keratitis in resistant (cornea-healing) BALB/c mice...

..To determine the effects of silencing Toll-like receptor (TLR) 9 signaling in Pseudomonas aeruginosa keratitis...

..These studies suggest that adequate expression of TIMP-1 protects against BM and stromal degradation via multiple processes...

..The antibody studies in this report suggest that the decrease in laminin-5 content in hypoxic matrix, relative to matrix secreted by normoxic corneal epithelium, may be responsible for increased bacterial adhesion...

..Remarkably, after 12 or 30 days of continuous CL wear, there was no significant up-regulation in lens wearing corneas for any of the cytokines-chemokines tested...

..To achieve these aims, molecular microbiological, immunological and biochemical methods will be used. ..

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..Ultimately, the findings from this proposal will be useful clinically in development of better treatments to reduce bacterial keratitis and prevent blindness. ..

..aeruginosa keratitis and should lead to better characterization of molecules which are potential targets for more effective treatment of corneal inflammation. ..

..abstract_text> ..

..It is expected that the findings will reveal potential targets for early intervention and/or treatment of P. aeruginosa keratitis. ..

..The use of the eye allows one to study a specific restricted organ system, thereby simplifying experimental design and data interpretation...

..The studies proposed will be of value in the development of immunotherapeutics and/or receptor analogs which either alone, or in concert, will serve to prevent or lessen bacterial infectivity and subsequent corneal inflammatory disease...

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