Abstract:
PURPOSE:The secreted Ly6/uPAR-related protein-1 (Slurp1), associated with the hyperkeratotic disorder mal de Meleda, is abundantly expressed in corneas. Here, we examine its corneal expression and functions. METHODS:Gene expression was quantified by quantitative PCR (qPCR), immunoblots, and immunofluorescent staining. Effect of Kruppel-like factor 4 (Klf4) on Slurp1 promoter was evaluated by chromatin immunoprecipitation (ChIP) and transient transfections. Adenoviral vectors were used to express Slurp1 in corneas. Leukocytic infiltration in bacterial lipopolysaccharide (LPS)-, herpes simplex virus type 1 (HSV-1)-, or adenovirus (serotype 5)-treated mouse corneas was characterized by flow cytometry. RESULTS:Corneal expression of Slurp1 increased sharply upon mouse eyelid opening, concurrent with the elevated expression of Klf4. Slurp1 was significantly decreased in Klf4 conditional null (Klf4CN) corneas that displayed elevated expression of cytokines and cytokine receptors, as well as neutrophil influx consistent with a proinflammatory environment. In additional models of corneal inflammation, Slurp1 expression was abrogated within 24 hours of LPS injection or HSV-1 or adenoviral infection, accompanied by a predominantly neutrophilic infiltrate. Neutrophilic infiltration was enhanced in HSV-1-infected Klf4CN corneas lacking Slurp1. SLURP1 promoter activity was stimulated by KLF4, suppressed by IL-4, IL-13, and TNFα, and unperturbed by IFN-γ. Slurp1 downregulation and neutrophil influx were comparable in HSV-1-infected wild-type (WT) and Ifng-/- mouse corneas. Mouse corneas infected with Slurp1-expressing adenoviral vectors displayed reduced signs of inflammation and restricted neutrophilic infiltration compared with those infected with control vectors. CONCLUSIONS:Klf4 regulates the expression of Slurp1, a key immunomodulatory peptide that is abundantly expressed in healthy corneas and is downregulated in proinflammatory conditions.
journal_name
Invest Ophthalmol Vis Scijournal_title
Investigative ophthalmology & visual scienceauthors
Swamynathan S,Buela KA,Kinchington P,Lathrop KL,Misawa H,Hendricks RL,Swamynathan SKdoi
10.1167/iovs.12-10759subject
Has Abstractpub_date
2012-12-19 00:00:00pages
8433-46issue
13eissn
0146-0404issn
1552-5783pii
iovs.12-10759journal_volume
53pub_type
杂志文章abstract:PURPOSE:To develop an eye-motion-tracking optical coherence tomographic (OCT) method and assess its effect on image registration and nerve fiber layer (NFL) thickness measurement reproducibility. METHODS:A system capable of tracking common fundus features based on reflectance changes was integrated into a commercial O...
journal_title:Investigative ophthalmology & visual science
pub_type: 杂志文章
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journal_title:Investigative ophthalmology & visual science
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doi:
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abstract:PURPOSE:To evaluate the role of manganese superoxide dismutase (Mn-SOD) and copper/zinc superoxide dismutase (Cu/Zn-SOD) in cellular protection of the optic nerve against the oxidative injury that contributes to demyelination in experimental allergic encephalomyelitis (EAE). METHODS:Immunocytochemistry for Mn-SOD and ...
journal_title:Investigative ophthalmology & visual science
pub_type: 杂志文章
doi:
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journal_title:Investigative ophthalmology & visual science
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更新日期:2000-12-01 00:00:00
abstract:PURPOSE:To explore connexin43 (Cx43) knockdown as an efficient treatment for corneal endothelial injury in an in vivo rat corneal scrape injury model. METHODS:Scrape injury was induced in the corneal endothelium, and immunolabeling (ZO-1, alpha-SMA, Cx43) was performed to analyze changes in Cx43 expression during woun...
journal_title:Investigative ophthalmology & visual science
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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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journal_title:Investigative ophthalmology & visual science
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journal_title:Investigative ophthalmology & visual science
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doi:
更新日期:1986-04-01 00:00:00
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更新日期:2008-10-01 00:00:00
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journal_title:Investigative ophthalmology & visual science
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doi:
更新日期:1985-07-01 00:00:00
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journal_title:Investigative ophthalmology & visual science
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doi:
更新日期:1983-10-01 00:00:00
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journal_title:Investigative ophthalmology & visual science
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doi:
更新日期:2001-09-01 00:00:00
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doi:
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更新日期:2010-01-01 00:00:00
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更新日期:2015-12-01 00:00:00
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更新日期:2009-09-01 00:00:00
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journal_title:Investigative ophthalmology & visual science
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doi:
更新日期:2000-04-01 00:00:00
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journal_title:Investigative ophthalmology & visual science
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doi:
更新日期:1983-09-01 00:00:00
abstract::The lacrimal gland is a functional part of the mucosal immune system and is populated by lymphoid cells that begin to appear early in neonatal development. To define the events controlling the accumulation of these cells, an in vitro adherence assay was used to investigate the interactions of lymphocyte populations wi...
journal_title:Investigative ophthalmology & visual science
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更新日期:1990-08-01 00:00:00