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Klf4 regulates the expression of Slurp1, which functions as an immunomodulatory peptide in the mouse cornea.

ABSTRACT: 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.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.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 TNF?, and unperturbed by IFN-?. 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.Klf4 regulates the expression of Slurp1, a key immunomodulatory peptide that is abundantly expressed in healthy corneas and is downregulated in proinflammatory conditions.

SUBMITTER: Swamynathan S

PROVIDER: S-EPMC4113333 | biostudies-literature | 2012 Dec

REPOSITORIES: biostudies-literature

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Klf4 regulates the expression of Slurp1, which functions as an immunomodulatory peptide in the mouse cornea.

Swamynathan Sudha S Buela Kristine-Ann KA Kinchington Paul P Lathrop Kira L KL Misawa Hidemi H Hendricks Robert L RL Swamynathan Shivalingappa K SK

Investigative ophthalmology & visual science 20121219 13

<h4>Purpose</h4>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.<h4>Methods</h4>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 ...[more]

PMID: 23139280

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Dataset Information

Klf4 regulates the expression of Slurp1, which functions as an immunomodulatory peptide in the mouse cornea.

Publications

Klf4 regulates the expression of Slurp1, which functions as an immunomodulatory peptide in the mouse cornea.

Similar Datasets

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