title: MMP-8 Is Critical for Dexamethasone Therapy in Alkali-Burned Corneas Under Dry Eye Conditions.
abstract: Our previous studies have shown that Dexamethasone (Dex) reduced the expression of matrix-metalloproteinases (MMPs -1,-3,-9,-13), IL-1β and IL-6, while it significantly increased MMP-8 mRNA transcripts in a concomitant dry eye and corneal alkali burn murine model (CM). To investigate if MMP-8 induction is responsible for some of the protective effects of Dex in CM, MMP-8 knock out mice (MMP-8KO) were subjected to the CM for 2 or 5 days and topically treated either with 2 μl of 0.1% Dexamethasone (Dex), or saline QID. A separate group of C57BL/6 mice were topically treated with Dex or BSS and received either 100 nM CAM12 (MMP-8 inhibitor) or vehicle IP, QD. Here we demonstrate that topical Dex treated MMP-8KO mice subjected to CM showed reduced corneal clarity, increased expression of inflammatory mediators (IL-6, CXCL1, and MMP-1 mRNA) and increased neutrophil infiltration at 2D and 5D compared to Dex treated WT mice. C57BL/6 mice topically treated with Dex and CAM12 IP recapitulated findings seen with MMP-8KO mice. These results suggest that some of the anti-inflammatory effects of Dex are mediated through increased MMP-8 expression. J. Cell. Physiol. 231: 2506-2516, 2016. © 2016 Wiley Periodicals, Inc.
authors.affiliation: Department of Ophthalmology, Baylor College of Medicine, Houston, Texas.
authors.forename: Fang
authors.initials: F
authors.lastname: Bian
authors.affiliation: Department of Ophthalmology, Baylor College of Medicine, Houston, Texas.
authors.forename: Changjun
authors.initials: C
authors.lastname: Wang
authors.affiliation: Department of Ophthalmology, Baylor College of Medicine, Houston, Texas.
authors.forename: Johanna
authors.initials: J
authors.lastname: Tukler-Henriksson
authors.affiliation: Department of Ophthalmology, Baylor College of Medicine, Houston, Texas.
authors.forename: Stephen C
authors.initials: SC
authors.lastname: Pflugfelder
authors.affiliation: Division of Immunology, Transplants and Infectious Diseases, San Raffaele Scientific Institute, Milan, Italy.
authors.forename: Caterina
authors.initials: C
authors.lastname: Camodeca
authors.affiliation: Department of Pharmacy, Pisa University, Pisa, Italy.
authors.forename: Elisa
authors.initials: E
authors.lastname: Nuti
authors.affiliation: Department of Pharmacy, Pisa University, Pisa, Italy.
authors.forename: Armando
authors.initials: A
authors.lastname: Rossello
authors.affiliation: Department of Ophthalmology, Baylor College of Medicine, Houston, Texas.
authors.forename: De-Quan
authors.initials: DQ
authors.lastname: Li
authors.affiliation: Department of Ophthalmology, Baylor College of Medicine, Houston, Texas.
authors.forename: Cintia S
authors.initials: CS
authors.lastname: de Paiva
mesh_terms: D000468:Alkalies; D000818:Animals; D000893:Anti-Inflammatory Agents / Q000494:pharmacology / Q000627:therapeutic use; D002057:Burns, Chemical / Q000150:complications / Q000188:drug therapy* / Q000201:enzymology*; D003315:Cornea / Q000201:enzymology / Q000473:pathology*; D003890:Desiccation; D003907:Dexamethasone / Q000494:pharmacology / Q000627:therapeutic use*; D004195:Disease Models, Animal; D015352:Dry Eye Syndromes / Q000150:complications* / Q000201:enzymology; D005126:Eye Burns / Q000150:complications / Q000188:drug therapy* / Q000201:enzymology*; D005260:Female; D020784:Matrix Metalloproteinase 8 / Q000172:deficiency / Q000235:genetics / Q000378:metabolism*; D061965:Matrix Metalloproteinase Inhibitors / Q000494:pharmacology / Q000627:therapeutic use; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D020556:Neutrophil Infiltration / Q000187:drug effects; D009504:Neutrophils / Q000187:drug effects / Q000378:metabolism; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D013312:Stress, Physiological
chemical_list: D000468:Alkalies; D000893:Anti-Inflammatory Agents; D061965:Matrix Metalloproteinase Inhibitors; D012333:RNA, Messenger; D003907:Dexamethasone; D020784:Matrix Metalloproteinase 8