Document Detail

Effects of VIP on corneal reconstitution and homeostasis following Pseudomonas aeruginosa induced keratitis.
MedLine Citation:
PMID:  23036997     Owner:  NLM     Status:  MEDLINE    
PURPOSE: Studies from our laboratory have demonstrated that vasoactive intestinal peptide (VIP) directly converts the normally susceptible C57BL/6J (B6) mouse to resistant after ocular infection through modulation of the inflammatory response. This study examines mechanisms by which VIP influences the healing phase following infection--specifically reconstitution of the extracellular matrix (ECM).
METHODS: B6 mice received daily intraperitoneal (IP) injections of VIP, while control mice were similarly injected with sterile phosphate buffered saline (PBS). Real-time RT-PCR, ELISA, and immunofluorescent staining were used to assess the effects of VIP treatment on ECM molecule expression after Pseudomonas aeruginosa-induced keratitis. We also compared the effect of VIP treatment on lipopolysaccharide (LPS)-stimulated B6- and BALB/c-derived fibroblasts.
RESULTS: In vivo analyses revealed that VIP treatment of P. aeruginosa-infected B6 corneas led to a significant increase in ECM molecules associated with healing/homeostasis, while those associated with ECM degradation were significantly down-regulated when compared to wild-type (WT) controls. In vitro studies revealed that VIP treatment of lipopolysaccharide-stimulated fibroblasts derived from susceptible B6 and resistant BALB/c mice expressed distinct differences in ECM molecule expression, whereby the latter expressed higher levels of ECM molecules aimed at reconstitution. Furthermore, differential expression of VIP receptor-1/VIP receptor-2 (VIPR1/VIPR2) was observed between B6 and BALB/c after VIP treatment of LPS-stimulated fibroblasts.
CONCLUSIONS: VIP treatment functions to enhance ECM reconstitution, which appears to be carried out in large part by fibroblasts via VIPR2. Overall, the data from this study suggest that VIP not only regulates disease pathogenesis, but also functions to restore integrity of the corneal stroma.
Elizabeth A Berger; Kerry S Vistisen; Ronald P Barrett; Linda D Hazlett
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Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't     Date:  2012-11-01
Journal Detail:
Title:  Investigative ophthalmology & visual science     Volume:  53     ISSN:  1552-5783     ISO Abbreviation:  Invest. Ophthalmol. Vis. Sci.     Publication Date:  2012 Nov 
Date Detail:
Created Date:  2012-11-05     Completed Date:  2013-01-15     Revised Date:  2013-07-11    
Medline Journal Info:
Nlm Unique ID:  7703701     Medline TA:  Invest Ophthalmol Vis Sci     Country:  United States    
Other Details:
Languages:  eng     Pagination:  7432-9     Citation Subset:  IM    
Department of Anatomy and Cell Biology, Wayne State University School of Medicine, Detroit, Michigan 48201, USA.
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MeSH Terms
Cornea / drug effects,  metabolism,  pathology*
Disease Models, Animal
Down-Regulation / drug effects
Enzyme-Linked Immunosorbent Assay
Extracellular Matrix / drug effects,  genetics,  metabolism
Eye Infections, Bacterial / drug therapy*,  metabolism,  microbiology
Keratitis / drug therapy*,  metabolism,  microbiology
Mice, Inbred BALB C
Mice, Inbred C57BL
Neuroprotective Agents / pharmacology
Pseudomonas Infections / drug therapy*,  metabolism,  microbiology
Pseudomonas aeruginosa / isolation & purification*
RNA, Messenger / genetics
Receptors, Vasoactive Intestinal Peptide, Type II / drug effects,  genetics,  metabolism
Receptors, Vasoactive Intestinal Polypeptide, Type I / drug effects,  genetics,  metabolism
Reverse Transcriptase Polymerase Chain Reaction
Vasoactive Intestinal Peptide / pharmacology*
Grant Support
Reg. No./Substance:
0/Neuroprotective Agents; 0/RNA, Messenger; 0/Receptors, Vasoactive Intestinal Peptide, Type II; 0/Receptors, Vasoactive Intestinal Polypeptide, Type I; 0/Vipr1 protein, mouse; 0/Vipr2 protein, mouse; 37221-79-7/Vasoactive Intestinal Peptide

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine

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