title: Substance P in the corneal stroma regulates the severity of herpetic stromal keratitis lesions.
abstract: OBJECTIVE
  To determine whether substance P (SP) in herpes simplex virus-1 (HSV-1) infected cornea regulates the severity of herpetic stromal keratitis (HSK) lesions in a mouse model.
  
  
  METHODS
  C57BL/6 mice were infected ocularly with HSV-1 (RE). The corneas with HSK lesions, on Day 15 postinfection, were grouped on the basis of the corneal opacity as mild (≤2) or severe (>2). The amount of SP was determined in the corneas with mild or severe HSK lesions by enzyme immunosorbent assay (EIA) and confocal microscopy. Subconjunctival inoculation of spantide I, SP receptor antagonist, was carried out during the clinical phase of HSK. ELISA and flow cytometry were used to determine the level of cytokines, chemokines, and influx of immune cell types in the corneal lesions.
  
  
  RESULTS
  The authors determined a significantly higher level of SP in the corneas with severe HSK lesions in comparison with mild lesions. The corneas with a higher level of SP also exhibited higher amounts of proinflammatory cytokines (IL-6, IFN-γ) and chemokines (CCL3, CXCL2) when compared with the corneas with a lower level of SP. SP receptor NK1R expression was determined in CD45- and CD45+ cells in infected cornea. SP present in the corneal stroma of the eyes with severe HSK lesions colocalized with β-III tubulin(+) and IA(b+) cell types. Subconjunctival inoculation of spantide I during the clinical phase of HSK resulted in significant reduction in the corneal opacity and angiogenesis.
  
  
  CONCLUSIONS
  Collectively, these results demonstrate the relative contribution of substance P in regulating the clinical severity of HSK lesions in a mouse model.
authors.affiliation: Department of Biological Sciences, Oakland University, Rochester, Michigan, USA.
authors.forename: Brandon S
authors.initials: BS
authors.lastname: Twardy
authors.forename: Rudragouda
authors.initials: R
authors.lastname: Channappanavar
authors.forename: Susmit
authors.initials: S
authors.lastname: Suvas
mesh_terms: D000700:Analgesics / Q000494:pharmacology; D000818:Animals; D015496:CD4-Positive T-Lymphocytes / Q000473:pathology / Q000821:virology; D054405:Chemokine CCL3 / Q000378:metabolism; D054426:Chemokine CXCL2 / Q000378:metabolism; D003319:Corneal Stroma / Q000276:immunology / Q000378:metabolism* / Q000473:pathology; D004195:Disease Models, Animal; D005260:Female; D018259:Herpesvirus 1, Human; D015850:Interleukin-6 / Q000378:metabolism; D016849:Keratitis, Herpetic / Q000188:drug therapy / Q000276:immunology / Q000378:metabolism* / Q000473:pathology; D017493:Leukocyte Common Antigens / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D009389:Neovascularization, Pathologic / Q000188:drug therapy / Q000276:immunology; D009504:Neutrophils / Q000473:pathology / Q000821:virology; D018040:Receptors, Neurokinin-1 / Q000378:metabolism; D012720:Severity of Illness Index; D013373:Substance P / Q000031:analogs & derivatives / Q000378:metabolism* / Q000494:pharmacology; D014404:Tubulin / Q000378:metabolism; D019562:Viral Load / Q000502:physiology
chemical_list: D000700:Analgesics; C496534:Ccl3 protein, mouse; D054405:Chemokine CCL3; D054426:Chemokine CXCL2; C404915:Cxcl2 protein, mouse; D015850:Interleukin-6; D018040:Receptors, Neurokinin-1; D014404:Tubulin; D013373:Substance P; C042867:spantide; D017493:Leukocyte Common Antigens; C516770:Ptprc protein, mouse