Abstract:
PURPOSE:We explored the role of myeloid-related protein 8 and 14 (MRP8/14) in Pseudomonas aeruginosa (PA) keratitis. METHODS:MRP8/14 mRNA levels in human corneal scrapes and mouse corneas infected by PA were tested using real-time PCR. MRP8/14 protein expression in C57BL/6 (B6) corneas was confirmed using Western blot assay and immunohistochemistry. B6 mice were injected subconjunctivally with siRNA for MRP8/14, and then infected with PA. Bacterial plate counts and myeloperoxidase assays were used to determine the bacterial load and polymorphonuclear neutrophil (PMN) infiltration in infected B6 corneas. Pro-inflammatory cytokine levels in vivo and in vitro were examined with PCR and ELISA. In murine macrophage-like RAW264.7 cells, phagocytosis and bacterial killing were assessed using plate count assays, and reactive oxygen species (ROS) and nitric oxide (NO) levels were tested with flow cytometry and Griess assay, respectively. RESULTS:MRP8/14 expression levels were increased significantly in human corneal scrapes and B6 corneas after PA infection. Silencing of MRP8/14 in B6 corneas significantly reduced the severity of corneal disease, bacterial clearance, PMN infiltration, and pro-inflammatory cytokine expression after PA infection. In vitro studies demonstrated further that silencing of MRP8/14 suppressed pro-inflammatory cytokine production, bacterial killing, and ROS production, but not phagocytosis or NO production. CONCLUSIONS:Our study demonstrated a dual role for MRP8/14 in bacterial keratitis. Although MRP8/14 promotes bacterial clearance by enhancing ROS production, it functions more importantly as an inflammatory amplifier at the ocular surface by enhancing pro-inflammatory cytokine expression, thus contributing to the corneal susceptibility.
journal_name
Invest Ophthalmol Vis Scijournal_title
Investigative ophthalmology & visual scienceauthors
Deng Q,Sun M,Yang K,Zhu M,Chen K,Yuan J,Wu M,Huang Xdoi
10.1167/iovs.12-10172subject
Has Abstractpub_date
2013-02-01 00:00:00pages
1227-34issue
2eissn
0146-0404issn
1552-5783pii
iovs.12-10172journal_volume
54pub_type
杂志文章abstract:PURPOSE:Elevated levels of C-reactive protein (CRP), a proinflammatory marker, are associated with systemic vascular disorders. In addition, clinical studies have implicated that elevated CRP is an independent risk factor for diabetic retinopathy and age-related macular degeneration. However, the direct effect of CRP o...
journal_title:Investigative ophthalmology & visual science
pub_type: 杂志文章
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journal_title:Investigative ophthalmology & visual science
pub_type: 杂志文章
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journal_title:Investigative ophthalmology & visual science
pub_type: 杂志文章
doi:
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journal_title:Investigative ophthalmology & visual science
pub_type: 杂志文章,随机对照试验
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更新日期:2011-10-28 00:00:00
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journal_title:Investigative ophthalmology & visual science
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doi:
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journal_title:Investigative ophthalmology & visual science
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doi:
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更新日期:2014-12-16 00:00:00
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journal_title:Investigative ophthalmology & visual science
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doi:
更新日期:2000-02-01 00:00:00
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journal_title:Investigative ophthalmology & visual science
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doi:
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journal_title:Investigative ophthalmology & visual science
pub_type: 杂志文章
doi:
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更新日期:2010-02-01 00:00:00
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journal_title:Investigative ophthalmology & visual science
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doi:
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journal_title:Investigative ophthalmology & visual science
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doi:
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更新日期:2008-06-01 00:00:00
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journal_title:Investigative ophthalmology & visual science
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doi:
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doi:
更新日期:2001-11-01 00:00:00
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journal_title:Investigative ophthalmology & visual science
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更新日期:2012-05-04 00:00:00
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pub_type: 临床试验,杂志文章,随机对照试验
doi:
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