PMID- 30597991
OWN - NLM
STAT- MEDLINE
DCOM- 20190221
LR  - 20200225
IS  - 1420-3049 (Electronic)
IS  - 1420-3049 (Linking)
VI  - 24
IP  - 1
DP  - 2018 Dec 29
TI  - PPARalpha Agonist Suppresses Inflammation after Corneal Alkali Burn by Suppressing 
      Proinflammatory Cytokines, MCP-1, and Nuclear Translocation of NF-kappaB.
LID - 10.3390/molecules24010114 [doi]
LID - 114
AB  - We investigated the effect of a peroxisome proliferator-activated receptor alpha 
      (PPARalpha) agonist after corneal alkali injury. Fenofibrate 0.05% (PPARalpha agonist 
      group) or vehicle (Vehicle group) was topically instilled onto the rat cornea 
      after injury. Histological, immunohistochemical, and real-time reverse 
      transcription PCR analyses were performed. PPARalpha-positive cells were observed 
      among basal cells of the corneal epithelium in normal and alkali-burned corneas. 
      The number of infiltrating neutrophils and macrophages at the corneal limbus was 
      lower in the PPARalpha agonist group. Interleukin-1beta (IL-1beta), IL-6, IL-8, monocyte 
      chemoattractant protein-1 (MCP-1), and vascular endothelial growth factor-An mRNA 
      expression was suppressed in the PPARalpha agonist group compared to the Vehicle 
      group. mRNA levels of nuclear factor kappa B (NF-kappaB) in corneal tissue were not 
      different. However, NF-kappaB was expressed in the cytoplasm of basal cells in the 
      PPARalpha agonist group and in the nucleus in the Vehicle group. MCP-1 was more 
      weakly expressed in the PPARalpha agonist group. The PPARalpha agonist inhibited 
      inflammation during the early phase after injury. Anti-inflammatory effects of 
      the PPARalpha agonist included prevention of up-regulation of proinflammatory 
      cytokines and MCP-1, and prevention of inflammatory cell infiltration into the 
      injured cornea. Thus, a PPARalpha agonist may be a promising treatment for corneal 
      injury.
FAU - Nakano, Yuichiro
AU  - Nakano Y
AD  - Department of Ophthalmology, Nippon Medical School, Tokyo 113-8603, Japan. 
      nakano1212@nms.ac.jp.
AD  - Department of Analytic Human Pathology, Nippon Medical School, Tokyo 113-8602, 
      Japan. nakano1212@nms.ac.jp.
FAU - Uchiyama, Masaaki
AU  - Uchiyama M
AD  - Department of Ophthalmology, Nippon Medical School, Tokyo 113-8603, Japan. 
      uchiyama@nms.ac.jp.
AD  - Department of Analytic Human Pathology, Nippon Medical School, Tokyo 113-8602, 
      Japan. uchiyama@nms.ac.jp.
FAU - Arima, Takeshi
AU  - Arima T
AD  - Department of Ophthalmology, Nippon Medical School, Tokyo 113-8603, Japan. 
      takesuiii0714@nms.ac.jp.
AD  - Department of Analytic Human Pathology, Nippon Medical School, Tokyo 113-8602, 
      Japan. takesuiii0714@nms.ac.jp.
FAU - Nagasaka, Shinya
AU  - Nagasaka S
AD  - Department of Analytic Human Pathology, Nippon Medical School, Tokyo 113-8602, 
      Japan. 3mousquetaires51a@gmail.com.
FAU - Igarashi, Tsutomu
AU  - Igarashi T
AUID- ORCID: 0000-0002-7467-6746
AD  - Department of Ophthalmology, Nippon Medical School, Tokyo 113-8603, Japan. 
      tutomu@nms.ac.jp.
FAU - Shimizu, Akira
AU  - Shimizu A
AUID- ORCID: 0000-0002-4364-9251
AD  - Department of Analytic Human Pathology, Nippon Medical School, Tokyo 113-8602, 
      Japan. ashimizu@nms.ac.jp.
FAU - Takahashi, Hiroshi
AU  - Takahashi H
AD  - Department of Ophthalmology, Nippon Medical School, Tokyo 113-8603, Japan. 
      tash@nms.ac.jp.
LA  - eng
PT  - Journal Article
DEP - 20181229
PL  - Switzerland
TA  - Molecules
JT  - Molecules (Basel, Switzerland)
JID - 100964009
RN  - 0 (Alkalies)
RN  - 0 (Biomarkers)
RN  - 0 (Chemokine CCL2)
RN  - 0 (Cytokines)
RN  - 0 (Inflammation Mediators)
RN  - 0 (NF-kappa B)
RN  - 0 (PPAR alpha)
SB  - IM
MH  - Alkalies/adverse effects
MH  - Animals
MH  - Biomarkers
MH  - Chemokine CCL2/*metabolism
MH  - Cytokines/*metabolism
MH  - Disease Models, Animal
MH  - Immunohistochemistry
MH  - Inflammation Mediators/*metabolism
MH  - Keratitis/*etiology/*metabolism
MH  - Macrophages/drug effects/immunology/metabolism/pathology
MH  - NF-kappa B/*metabolism
MH  - PPAR alpha/*agonists/metabolism
MH  - Protein Transport
MH  - Rats
PMC - PMC6337747
OTO - NOTNLM
OT  - IL-1beta
OT  - IkappaB-alpha
OT  - VEGF-A
OT  - fenofibrate
OT  - ophthalmic solution
COIS- The authors declare no conflicts of interest. The funding organization had no 
      role in the design or conduct of this research.
EDAT- 2019/01/02 06:00
MHDA- 2019/02/23 06:00
PMCR- 2018/12/29
CRDT- 2019/01/02 06:00
PHST- 2018/11/28 00:00 [received]
PHST- 2018/12/24 00:00 [revised]
PHST- 2018/12/24 00:00 [accepted]
PHST- 2019/01/02 06:00 [entrez]
PHST- 2019/01/02 06:00 [pubmed]
PHST- 2019/02/23 06:00 [medline]
PHST- 2018/12/29 00:00 [pmc-release]
AID - molecules24010114 [pii]
AID - molecules-24-00114 [pii]
AID - 10.3390/molecules24010114 [doi]
PST - epublish
SO  - Molecules. 2018 Dec 29;24(1):114. doi: 10.3390/molecules24010114.