title: MK2 inhibitor reduces alkali burn-induced inflammation in rat cornea.
abstract: MK2 activation by p38 MAPK selectively induces inflammation in various diseases. We determined if a MK2 inhibitor (MK2i), improves cornea wound healing by inhibiting inflammation caused by burning rat corneas with alkali. Our study, for the first time, demonstrated that MK2i inhibited alkali burn-induced MK2 activation as well as rises in inflammation based on: a) blunting rises in inflammatory index, inflammatory cell infiltration, ED1(+) macrophage and PMN(+) neutrophil infiltration; b) suppressing IL-6 and IL-1β gene expression along with those of macrophage inflammatory protein-1α (MIP-1α), intercellular adhesion molecule-1 (ICAM-1) and vascular cell adhesion molecule-1 (VCAM-1); c) reducing angiogenic gene expression levels and neovascularization (NV) whereas anti-angiogenic PEDF levels increased. In addition, this study found that MK2i did not affect human corneal epithelial cell (HCEC) proliferation and migration and had no detectable side effects on ocular surface integrity. Taken together, MK2i selectively inhibited alkali burn-induced corneal inflammation by blocking MK2 activation, these effects have clinical relevance in the treatment of inflammation related ocular surface diseases.
authors.affiliation: Eye Institute of Xiamen University, Fujian Provincial Key Laboratory of Ophthalmology and Visual Science, Xiamen, Fujian, China.
authors.forename: Yanfeng
authors.initials: Y
authors.lastname: Chen
authors.affiliation: Eye Institute of Xiamen University, Fujian Provincial Key Laboratory of Ophthalmology and Visual Science, Xiamen, Fujian, China.
authors.forename: Wenzhao
authors.initials: W
authors.lastname: Yang
authors.affiliation: Eye Institute of Xiamen University, Fujian Provincial Key Laboratory of Ophthalmology and Visual Science, Xiamen, Fujian, China.
authors.forename: Xiaobo
authors.initials: X
authors.lastname: Zhang
authors.affiliation: Eye Institute of Xiamen University, Fujian Provincial Key Laboratory of Ophthalmology and Visual Science, Xiamen, Fujian, China.
authors.forename: Shu
authors.initials: S
authors.lastname: Yang
authors.affiliation: Eye Institute of Xiamen University, Fujian Provincial Key Laboratory of Ophthalmology and Visual Science, Xiamen, Fujian, China.
authors.forename: Gao
authors.initials: G
authors.lastname: Peng
authors.affiliation: Department of Basic Medical Sciences, Cancer Research Center, Medical College, Xiamen University, Xiamen, China.
authors.forename: Ting
authors.initials: T
authors.lastname: Wu
authors.affiliation: Eye Institute of Xiamen University, Fujian Provincial Key Laboratory of Ophthalmology and Visual Science, Xiamen, Fujian, China.
authors.forename: Yueping
authors.initials: Y
authors.lastname: Zhou
authors.affiliation: Eye Institute of Xiamen University, Fujian Provincial Key Laboratory of Ophthalmology and Visual Science, Xiamen, Fujian, China.
authors.forename: Caihong
authors.initials: C
authors.lastname: Huang
authors.affiliation: School of Ophthalmology and Optometry and Eye Hospital, Wenzhou Medical University, Wenzhou, Zhejiang, China.|State Key Laboratory Cultivation Base and Key Laboratory of Vision Science, Ministry of Health, People's Republic of China.|Zhejiang Provincial Key Laboratory of Ophthalmology and Optometry, Wenzhou, Zhejiang, China.
authors.forename: Peter S
authors.initials: PS
authors.lastname: Reinach
authors.affiliation: Eye Institute of Xiamen University, Fujian Provincial Key Laboratory of Ophthalmology and Visual Science, Xiamen, Fujian, China.|Affiliated Xiamen Eye Center of Xiamen University, Xiamen, Fujian, China.
authors.forename: Wei
authors.initials: W
authors.lastname: Li
authors.affiliation: Eye Institute of Xiamen University, Fujian Provincial Key Laboratory of Ophthalmology and Visual Science, Xiamen, Fujian, China.|Affiliated Xiamen Eye Center of Xiamen University, Xiamen, Fujian, China.
authors.forename: Zuguo
authors.initials: Z
authors.lastname: Liu
mesh_terms: D000468:Alkalies / Q000633:toxicity; D000818:Animals; D002057:Burns, Chemical / Q000188:drug therapy / Q000209:etiology / Q000473:pathology*; D002460:Cell Line; D049109:Cell Proliferation / Q000187:drug effects; D054405:Chemokine CCL3 / Q000235:genetics / Q000378:metabolism; D003315:Cornea / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D006801:Humans; D007249:Inflammation / Q000473:pathology / Q000517:prevention & control*; D018799:Intercellular Adhesion Molecule-1 / Q000235:genetics / Q000378:metabolism; D053583:Interleukin-1beta / Q000235:genetics / Q000378:metabolism; D015850:Interleukin-6 / Q000235:genetics / Q000378:metabolism; D047908:Intracellular Signaling Peptides and Proteins / Q000037:antagonists & inhibitors / Q000378:metabolism*; D008297:Male; D020556:Neutrophil Infiltration / Q000187:drug effects; D047428:Protein Kinase Inhibitors / Q000494:pharmacology* / Q000627:therapeutic use; D017346:Protein Serine-Threonine Kinases / Q000037:antagonists & inhibitors / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley; D015854:Up-Regulation / Q000187:drug effects; D019010:Vascular Cell Adhesion Molecule-1 / Q000235:genetics / Q000378:metabolism; D000099190:MAP-Kinase-Activated Kinase 2
chemical_list: D000468:Alkalies; D054405:Chemokine CCL3; D018799:Intercellular Adhesion Molecule-1; D053583:Interleukin-1beta; D015850:Interleukin-6; D047908:Intracellular Signaling Peptides and Proteins; D047428:Protein Kinase Inhibitors; D017346:Protein Serine-Threonine Kinases; D019010:Vascular Cell Adhesion Molecule-1; D000099190:MAP-Kinase-Activated Kinase 2