MK2 inhibitor reduces alkali burn-induced inflammation in rat cornea

Yanfeng Chen; Wenzhao Yang; Xiaobo Zhang; Shu Yang; Gao Peng; Ting Wu; Yueping Zhou; Caihong Huang; Peter S Reinach; Wei Li; Zuguo Liu

doi:10.1038/srep28145

MK2 inhibitor reduces alkali burn-induced inflammation in rat cornea

Sci Rep. 2016 Jun 22:6:28145. doi: 10.1038/srep28145.

Authors

Yanfeng Chen¹, Wenzhao Yang¹, Xiaobo Zhang¹, Shu Yang¹, Gao Peng¹, Ting Wu², Yueping Zhou¹, Caihong Huang¹, Peter S Reinach^{3

4

5}, Wei Li^{1

6}, Zuguo Liu^{1

6}

Affiliations

¹ Eye Institute of Xiamen University, Fujian Provincial Key Laboratory of Ophthalmology and Visual Science, Xiamen, Fujian, China.
² Department of Basic Medical Sciences, Cancer Research Center, Medical College, Xiamen University, Xiamen, China.
³ School of Ophthalmology and Optometry and Eye Hospital, Wenzhou Medical University, Wenzhou, Zhejiang, China.
⁴ State Key Laboratory Cultivation Base and Key Laboratory of Vision Science, Ministry of Health, People's Republic of China.
⁵ Zhejiang Provincial Key Laboratory of Ophthalmology and Optometry, Wenzhou, Zhejiang, China.
⁶ Affiliated Xiamen Eye Center of Xiamen University, Xiamen, Fujian, China.

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.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Alkalies / toxicity
Animals
Burns, Chemical / drug therapy
Burns, Chemical / etiology
Burns, Chemical / pathology*
Cell Line
Cell Proliferation / drug effects
Chemokine CCL3 / genetics
Chemokine CCL3 / metabolism
Cornea / drug effects*
Cornea / metabolism
Cornea / pathology
Humans
Inflammation / pathology
Inflammation / prevention & control*
Intercellular Adhesion Molecule-1 / genetics
Intercellular Adhesion Molecule-1 / metabolism
Interleukin-1beta / genetics
Interleukin-1beta / metabolism
Interleukin-6 / genetics
Interleukin-6 / metabolism
Intracellular Signaling Peptides and Proteins / antagonists & inhibitors
Intracellular Signaling Peptides and Proteins / metabolism*
Male
Neutrophil Infiltration / drug effects
Protein Kinase Inhibitors / pharmacology*
Protein Kinase Inhibitors / therapeutic use
Protein Serine-Threonine Kinases / antagonists & inhibitors
Protein Serine-Threonine Kinases / metabolism*
Rats
Rats, Sprague-Dawley
Up-Regulation / drug effects
Vascular Cell Adhesion Molecule-1 / genetics
Vascular Cell Adhesion Molecule-1 / metabolism

Substances

Alkalies
Chemokine CCL3
Interleukin-1beta
Interleukin-6
Intracellular Signaling Peptides and Proteins
Protein Kinase Inhibitors
Vascular Cell Adhesion Molecule-1
Intercellular Adhesion Molecule-1
MAP-kinase-activated kinase 2
Protein Serine-Threonine Kinases