論文 - 詳細
RRC ID | 65749 |
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著者 | Chen Y, Yang W, Zhang X, Yang S, Peng G, Wu T, Zhou Y, Huang C, Reinach PS, Li W, Liu Z. |
タイトル | MK2 inhibitor reduces alkali burn-induced inflammation in rat cornea. |
ジャーナル | Sci Rep |
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. |
巻・号 | 6 |
ページ | 28145 |
公開日 | 2016-6-22 |
DOI | 10.1038/srep28145 |
PII | srep28145 |
PMID | 27329698 |
PMC | PMC4916419 |
MeSH | 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 |
IF | 3.998 |
リソース情報 | |
ヒト・動物細胞 | HCE-T(RCB2280) |