PMID- 23139280
OWN - NLM
STAT- MEDLINE
DCOM- 20130214
LR  - 20211203
IS  - 1552-5783 (Electronic)
IS  - 0146-0404 (Print)
IS  - 0146-0404 (Linking)
VI  - 53
IP  - 13
DP  - 2012 Dec 19
TI  - Klf4 regulates the expression of Slurp1, which functions as an immunomodulatory 
      peptide in the mouse cornea.
PG  - 8433-46
LID - 10.1167/iovs.12-10759 [doi]
AB  - 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 TNFalpha, and unperturbed by IFN-gamma. 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.
FAU - Swamynathan, Sudha
AU  - Swamynathan S
AD  - Department of Ophthalmology, University of Pittsburgh, Pittsburgh, Pennsylvania 
      15213, USA. Swamynathansk@upmc.edu
FAU - Buela, Kristine-Ann
AU  - Buela KA
FAU - Kinchington, Paul
AU  - Kinchington P
FAU - Lathrop, Kira L
AU  - Lathrop KL
FAU - Misawa, Hidemi
AU  - Misawa H
FAU - Hendricks, Robert L
AU  - Hendricks RL
FAU - Swamynathan, Shivalingappa K
AU  - Swamynathan SK
LA  - eng
GR  - K22 EY016875/EY/NEI NIH HHS/United States
GR  - EY10359/EY/NEI NIH HHS/United States
GR  - R01 EY015291/EY/NEI NIH HHS/United States
GR  - R01 EY010359/EY/NEI NIH HHS/United States
GR  - P30 EY08098/EY/NEI NIH HHS/United States
GR  - P30 EY008098/EY/NEI NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
DEP - 20121219
PL  - United States
TA  - Invest Ophthalmol Vis Sci
JT  - Investigative ophthalmology & visual science
JID - 7703701
RN  - 0 (Antigens, Ly)
RN  - 0 (Cytokines)
RN  - 0 (Growth Inhibitors)
RN  - 0 (Immunologic Factors)
RN  - 0 (KLF4 protein, human)
RN  - 0 (Klf4 protein, mouse)
RN  - 0 (Kruppel-Like Factor 4)
RN  - 0 (Kruppel-Like Transcription Factors)
RN  - 0 (Lipopolysaccharides)
RN  - 0 (SLURP-1 protein, mouse)
RN  - EC 3.4.21.73 (Urokinase-Type Plasminogen Activator)
RN  - Neutrophil Chemotactic Response, Abnormal
SB  - IM
MH  - Adenoviridae/genetics
MH  - Animals
MH  - Antigens, Ly/*genetics/metabolism
MH  - Base Sequence
MH  - Chromatin Immunoprecipitation
MH  - Cornea/*metabolism
MH  - Cytokines/pharmacology
MH  - Female
MH  - Flow Cytometry
MH  - Fluorescent Antibody Technique, Indirect
MH  - Gene Expression Regulation/*physiology
MH  - Genetic Vectors
MH  - Growth Inhibitors/*physiology
MH  - Herpesvirus 1, Human/physiology
MH  - Immune System Diseases
MH  - Immunoblotting
MH  - Immunologic Factors/genetics/metabolism
MH  - Keratitis, Herpetic/genetics/metabolism
MH  - Kruppel-Like Factor 4
MH  - Kruppel-Like Transcription Factors/*physiology
MH  - Leukocyte Disorders
MH  - Lipopolysaccharides/toxicity
MH  - Male
MH  - Mice
MH  - Mice, Inbred BALB C
MH  - Mice, Knockout
MH  - Molecular Sequence Data
MH  - Polymerase Chain Reaction
MH  - Transfection
MH  - Urokinase-Type Plasminogen Activator/*genetics/metabolism
PMC - PMC4113333
COIS- Disclosure: S. Swamynathan, None; K.-A. Buela, None; P. Kinchington, None; K.L. 
      Lathrop, None; H. Misawa, None; R.L. Hendricks, None; S.K. Swamynathan, None
EDAT- 2012/11/10 06:00
MHDA- 2013/02/15 06:00
PMCR- 2013/06/01
CRDT- 2012/11/10 06:00
PHST- 2012/11/10 06:00 [entrez]
PHST- 2012/11/10 06:00 [pubmed]
PHST- 2013/02/15 06:00 [medline]
PHST- 2013/06/01 00:00 [pmc-release]
AID - iovs.12-10759 [pii]
AID - 10.1167/iovs.12-10759 [doi]
PST - epublish
SO  - Invest Ophthalmol Vis Sci. 2012 Dec 19;53(13):8433-46. doi: 
      10.1167/iovs.12-10759.