Further studies on the role of IL-12 in Pseudomonas aeruginosa corneal infection

Hazlett, Linda D.; Huang, Xi; McClellan, Sharon A.; Barrett, Ronald P.

doi:10.1038/sj.eye.6700558

Cited by 37 publications

(50 citation statements)

References 27 publications

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“…Whole eyes were enucleated at 5 days p.i. from PBS-and rVIPtreated B6 mice (n ϭ 3/group), fixed, dehydrated, and embedded in paraffin as previously described (17), then stored at Ϫ20°C for immunofluorescent analysis. Ten-micrometer-thick sections were deparaffinized, then rehydrated through graded alcohols.…”

Section: Immunofluorescent Stainingmentioning

confidence: 99%

Vasoactive Intestinal Peptide Balances Pro- and Anti-Inflammatory Cytokines in the Pseudomonas aeruginosa-Infected Cornea and Protects against Corneal Perforation

Szliter

Lighvani

Barrett

et al. 2007

The Journal of Immunology

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Corneal infection with Pseudomonas aeruginosa perforates the cornea in susceptible C57BL/6 (B6), but not resistant BALB/c, mice. To determine whether vasoactive intestinal peptide (VIP) played a role in development of the resistant response, protein expression levels were tested by immunocytochemistry and enzyme immunoassay in BALB/c and B6 corneas. Both mouse strains showed constitutive expression of corneal VIP protein and nerve fiber distribution. However, disparate expression patterns were detected in the cornea after infection. VIP protein was elevated significantly in BALB/c over B6 mice at 5 and 7 days postinfection. Therefore, B6 mice were injected with rVIP and subsequently demonstrated decreased corneal opacity and resistance to corneal perforation compared with PBS controls. rVIP- vs PBS-treated B6 mice also demonstrated down-regulation of corneal mRNA and/or protein levels for proinflammatory cytokines/chemokines: IFN-γ, IL-1β, MIP-2, and TNF-α, whereas anti-inflammatory mediators, IL-10 and TGF-β1, were up-regulated. Treatment with rVIP decreased NO levels and polymorphonuclear neutrophil (PMN) number. To further define the role of VIP, peritoneal macrophages (Mφ) and PMN from BALB/c and B6 mice were stimulated with LPS and treated with rVIP. Treatment of LPS-stimulated Mφ from both mouse strains resulted in decreased IL-1β and MIP-2 protein levels; PMN responded similarly. Both cell types also displayed a strain-dependent differential response to rVIP, whereby B6 Mφ/PMN responded only to a higher concentration of VIP compared with cells from BALB/c mice. These data provide evidence that neuroimmune regulation of the cytokine network and host inflammatory cells functions to promote resistance against P. aeruginosa corneal infection.

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Section: Immunofluorescent Stainingmentioning

confidence: 99%

Vasoactive Intestinal Peptide Balances Pro- and Anti-Inflammatory Cytokines in the Pseudomonas aeruginosa-Infected Cornea and Protects against Corneal Perforation

Szliter

Lighvani

Barrett

et al. 2007

The Journal of Immunology

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“…We also found that in B6 mice, either sustained IL-12-driven IFN-c production or endogenous absence of IL-12, resulting in reduced IFN-c mRNA levels, leads to corneal perforation [7]. In contrast, studies using similar procedures failed to detect IL-12 in the infected cornea of BALB/c mice that control infection and restore corneal clarity [7,8], suggesting that these animals regulate IFN-c production through IL-12-independent mechanisms, resulting in less corneal toxicity and destruction. Nonetheless, BALB/c mice can respond to exogenously injected rIL-12 and perforation results in infected mice [9].…”

Section: Introductionmentioning

confidence: 52%

“…Recently, IL-12 has been demonstrated in the cornea of susceptible B6 mice by RT-PCR and protein analyses [7]. We also found that in B6 mice, either sustained IL-12-driven IFN-c production or endogenous absence of IL-12, resulting in reduced IFN-c mRNA levels, leads to corneal perforation [7].…”

Section: Introductionmentioning

confidence: 68%

“…In contrast, studies using similar procedures failed to detect IL-12 in the infected cornea of BALB/c mice that control infection and restore corneal clarity [7,8], suggesting that these animals regulate IFN-c production through IL-12-independent mechanisms, resulting in less corneal toxicity and destruction. Nonetheless, BALB/c mice can respond to exogenously injected rIL-12 and perforation results in infected mice [9]. Most importantly, we found that it is IL-18 that tightly regulates IFN-c production in the cornea of resistant BALB/c mice and that either neutralization of IL-18 or endogenous lack of IFN-c results in increased bacterial load and corneal perforation [10].…”

Section: Introductionmentioning

confidence: 99%

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Substance P regulates natural killer cell interferon‐γ production and resistance to Pseudomonas aeruginosa infection

et al. 2005

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Studies have shown that after Pseudomonas aeruginosa (P. aeruginosa) corneal infection, BALB/c mice that are capable of resolving the disease, locally produce IFN-c. As T cells are not detected in the infected cornea of these mice, antibody depletion was used to test whether NK cells produce the cytokine. After depletion, decreased corneal IFN-c mRNA and increased disease severity, bacterial load, and PMN infiltrate resulted. Further work determined if substance P (SP), a pro-inflammatory neuropeptide, participated in regulation of this response. To this end, mice were treated with the SP antagonist, spantide I that blocks SP interaction with neurokinin-1, its major receptor. The treatment significantly decreased corneal IFN-c and IL-18 protein levels and corneal perforation resulted. In vitro experiments using isolated splenic NK cells confirmed their ability to respond to IL-18 and SP and to secrete IFN-c protein. We conclude: that for development of the BALB/c resistance response, NK cells are required to produce IFN-c; that the cells express the neurokinin-1 receptor; and that SP directly regulates IFN-c production through this receptor. The data suggest a unique link between the nervous system and development of innate immunity in the cornea.

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“…45 In addition to organism factors, host lysosomal enzymes and oxidative substances produced by neutrophils, keratocytes, and epithelial cells may significantly contribute to the destruction caused by Pseudomonas keratitis. 46 Two eukaryotic gelatinase species have been characterized, including a type IV collagenase (72 kDa) and a type V collagenase (90-100 kDa).…”

mentioning

confidence: 99%

Management of bacterial keratitis: beyond exorcism towards consideration of organism and host factors

O’Brien

2003

Eye

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Further studies on the role of IL-12 in Pseudomonas aeruginosa corneal infection

Cited by 37 publications

References 27 publications

Vasoactive Intestinal Peptide Balances Pro- and Anti-Inflammatory Cytokines in the Pseudomonas aeruginosa-Infected Cornea and Protects against Corneal Perforation

Vasoactive Intestinal Peptide Balances Pro- and Anti-Inflammatory Cytokines in the Pseudomonas aeruginosa-Infected Cornea and Protects against Corneal Perforation

Substance P regulates natural killer cell interferon‐γ production and resistance to Pseudomonas aeruginosa infection

Management of bacterial keratitis: beyond exorcism towards consideration of organism and host factors

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