PMID- 28501766 OWN - NLM STAT- MEDLINE DCOM- 20180312 LR - 20180312 IS - 1878-1705 (Electronic) IS - 1567-5769 (Linking) VI - 48 DP - 2017 Jul TI - Therapeutic effects of zerumbone in an alkali-burned corneal wound healing model. PG - 126-134 LID - S1567-5769(17)30176-5 [pii] LID - 10.1016/j.intimp.2017.05.005 [doi] AB - Cornea is an avascular transparent tissue. Ocular trauma caused by a corneal alkali burn induces corneal neovascularization (CNV), inflammation, and fibrosis, leading to vision loss. The purpose of this study was to examine the effects of Zerumbone (ZER) on corneal wound healing caused by alkali burns in mice. CNV was induced by alkali-burn injury in BALB/C female mice. Topical ZER (three times per day, 3mul each time, at concentrations of 5, 15, and 30muM) was applied to treat alkali-burned mouse corneas for 14 consecutive days. Histopathologically, ZER treatment suppressed alkali burn-induced CNV and decreased corneal epithelial defects induced by alkali burns. Corneal tissue treated with ZER showed reduced mRNA levels of pro-angiogenic genes, including vascular endothelial growth factor, matrix metalloproteinase-2 and 9, and pro-fibrotic factors such as alpha smooth muscle actin and transforming growth factor-1 and 2. Immunohistochemical analysis demonstrated that the infiltration of F4/80 and/or CCR2 positive cells was significantly decreased in ZER-treated corneas. ZER markedly inhibited the mRNA and protein levels of monocyte chemoattractant protein-1 (MCP-1) in human corneal fibroblasts and murine peritoneal macrophages. Immunoblot analysis revealed that ZER decreased the activation of signal transducer and activator of transcription 3 (STAT3), with consequent reduction of MCP-1 production by these cells. In conclusion, topical administration of ZER accelerated corneal wound healing by inhibition of STAT3 and MCP-1 production. CI - Copyright (c) 2017. Published by Elsevier B.V. FAU - Kim, Jong Won AU - Kim JW AD - Biosafety Research Institute and Laboratory of Pathology (BK21 Plus Program), College of Veterinary Medicine, Chonbuk National University, Iksan, Republic of Korea. FAU - Jeong, Hyuneui AU - Jeong H AD - Biosafety Research Institute and Laboratory of Pathology (BK21 Plus Program), College of Veterinary Medicine, Chonbuk National University, Iksan, Republic of Korea. FAU - Yang, Myeon-Sik AU - Yang MS AD - Biosafety Research Institute and Laboratory of Pathology (BK21 Plus Program), College of Veterinary Medicine, Chonbuk National University, Iksan, Republic of Korea. FAU - Lim, Chae Woong AU - Lim CW AD - Biosafety Research Institute and Laboratory of Pathology (BK21 Plus Program), College of Veterinary Medicine, Chonbuk National University, Iksan, Republic of Korea. FAU - Kim, Bumseok AU - Kim B AD - Biosafety Research Institute and Laboratory of Pathology (BK21 Plus Program), College of Veterinary Medicine, Chonbuk National University, Iksan, Republic of Korea. Electronic address: bskims@jbnu.ac.kr. LA - eng PT - Journal Article DEP - 20170511 PL - Netherlands TA - Int Immunopharmacol JT - International immunopharmacology JID - 100965259 RN - 0 (Alkalies) RN - 0 (Chemokine CCL2) RN - 0 (STAT3 Transcription Factor) RN - 0 (Sesquiterpenes) RN - 471-05-6 (zerumbone) SB - IM MH - Alkalies MH - Animals MH - Burns, Chemical/*drug therapy/metabolism/pathology MH - Cell Line MH - Cells, Cultured MH - Chemokine CCL2/antagonists & inhibitors/genetics/metabolism MH - Cornea/drug effects/metabolism/pathology MH - Corneal Injuries/chemically induced/*drug therapy/metabolism/pathology MH - Corneal Neovascularization/chemically induced/*drug therapy/metabolism/pathology MH - Eye Burns/chemically induced/*drug therapy/metabolism/pathology MH - Female MH - Fibroblasts/drug effects/metabolism MH - Humans MH - Macrophages, Peritoneal/drug effects/metabolism MH - Mice, Inbred BALB C MH - STAT3 Transcription Factor/antagonists & inhibitors/metabolism MH - Sesquiterpenes/pharmacology/*therapeutic use MH - Wound Healing/drug effects OTO - NOTNLM OT - Alkali-burned injury OT - CCL2/MCP-1 OT - Cornea OT - STAT3 OT - Zerumbone EDAT- 2017/05/16 06:00 MHDA- 2018/03/13 06:00 CRDT- 2017/05/15 06:00 PHST- 2017/01/17 00:00 [received] PHST- 2017/04/17 00:00 [revised] PHST- 2017/05/04 00:00 [accepted] PHST- 2017/05/16 06:00 [pubmed] PHST- 2018/03/13 06:00 [medline] PHST- 2017/05/15 06:00 [entrez] AID - S1567-5769(17)30176-5 [pii] AID - 10.1016/j.intimp.2017.05.005 [doi] PST - ppublish SO - Int Immunopharmacol. 2017 Jul;48:126-134. doi: 10.1016/j.intimp.2017.05.005. Epub 2017 May 11.