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The infection results in IL-17A production, which contributes to CV in ways that together serve to shift the balance between corneal concentrations of vascular endothelial growth factor A (VEGF-A) and the soluble vascular endothelial growth factor receptor 1 molecule, which binds to VEGF-A and blocks its function (a so-called VEGF trap). Accordingly, animals lacking responses to IL-17A signaling, either because of IL-17 receptor A knockout or wild-type animals that received neutralizing mAb to IL-17A, had diminished CV, compared with controls. The procedures reduced VEGF-A protein levels but had no effect on the levels of soluble vascular endothelial growth factor receptor 1. Hence the VEGF trap was strengthened. IL-17A also caused increased CXCL1\/KC synthesis, which attracts neutrophils to the inflammatory site. Neutrophils further influenced the extent of CV by acting as an additional source of VEGF-A, as did metalloproteinase enzymes that degrade the soluble receptor, inhibiting its VEGF-blocking activity. Our results indicate that suppressing the expression of IL-17A, or increasing the activity of the VEGF trap, represents a useful approach to inhibiting CV and the control of an ocular lesion that is an important cause of human blindness.<\/jats:p>","DOI":"10.4049\/jimmunol.1102602","type":"journal-article","created":{"date-parts":[[2012,3,1]],"date-time":"2012-03-01T06:30:57Z","timestamp":1330583457000},"page":"3434-3446","source":"Crossref","is-referenced-by-count":73,"title":["IL-17A Differentially Regulates Corneal Vascular Endothelial Growth Factor (VEGF)-A and Soluble VEGF Receptor 1 Expression and Promotes Corneal Angiogenesis after Herpes Simplex Virus Infection"],"prefix":"10.1093","volume":"188","author":[{"given":"Amol","family":"Suryawanshi","sequence":"first","affiliation":[{"name":"Department of Pathobiology, College of Veterinary Medicine, University of Tennessee , Knoxville, TN 37996"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tamara","family":"Veiga-Parga","sequence":"additional","affiliation":[{"name":"Department of Pathobiology, College of Veterinary Medicine, University of Tennessee , Knoxville, TN 37996"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pradeep B J","family":"Reddy","sequence":"additional","affiliation":[{"name":"Department of Pathobiology, College of Veterinary Medicine, University of Tennessee , Knoxville, TN 37996"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Naveen K","family":"Rajasagi","sequence":"additional","affiliation":[{"name":"Department of Pathobiology, College of Veterinary Medicine, University of Tennessee , Knoxville, TN 37996"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Barry T","family":"Rouse","sequence":"additional","affiliation":[{"name":"Department of Pathobiology, College of Veterinary Medicine, University of Tennessee , Knoxville, TN 37996"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2012,4,1]]},"reference":[{"key":"2025032410010093300_r1","first-page":"264","article-title":"Corneal angiogenic privilege: angiogenic and antiangiogenic factors in corneal avascularity, vasculogenesis, and wound healing (an American Ophthalmological Society thesis)","volume":"104","author":"Azar","year":"2006","journal-title":"Trans. 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