PMID- 36739832
OWN - NLM
STAT- MEDLINE
DCOM- 20230308
LR  - 20230308
IS  - 1878-1705 (Electronic)
IS  - 1567-5769 (Linking)
VI  - 116
DP  - 2023 Mar
TI  - Upadacitinib inhibits corneal inflammation and neovascularization by suppressing 
      M1 macrophage infiltration in the corneal alkali burn model.
PG  - 109680
LID - S1567-5769(23)00003-6 [pii]
LID - 10.1016/j.intimp.2023.109680 [doi]
AB  - Alkali burn-induced corneal inflammation and subsequent corneal 
      neovascularization (CNV) are major causes of corneal opacity and vision loss. M1 
      macrophages play a central role in inflammation and CNV. Therefore, modulation of 
      M1 macrophage polarization is a promising strategy for corneal alkali burns. 
      Here, we illustrate the effect and underlying mechanisms of upadacitinib on 
      corneal inflammation and CNV induced by alkali burns in mice. The corneas of 
      BALB/c mice were administered with 1 M NaOH for 30 s and randomly assigned to the 
      vehicle group and the upadacitinib-treated group. Corneal opacity and corneal 
      epithelial defects were assessed clinically. Quantitative real-time PCR 
      (qRT-PCR), immunohistochemistry, and western blot analysis were performed to 
      detect M1 macrophage polarization and CD31(+) corneal blood vessels. The results 
      showed that upadacitinib notably decreased corneal opacity, and promoted corneal 
      wound healing. On day 7 and 14 after alkali burns, upadacitinib significantly 
      suppressed CNV. Corneal alkali injury caused M1 macrophage recruitment in the 
      cornea. In contrast to the vehicle, upadacitinib suppressed M1 macrophage 
      infiltration and decreased the mRNA expression levels of inducible nitric oxide 
      synthase (iNOS), monocyte chemotactic protein-1 (MCP-1), tumor necrosis 
      factor-alpha (TNF-alpha), interleukin (IL)-6, IL-1beta, and vascular endothelial growth 
      factor A (VEGF-A) in alkali-injured corneas. Moreover, upadacitinib 
      dose-dependently inhibited M1 macrophage polarization by suppressing interferon 
      (IFN)-gamma-/lipopolysaccharide-stimulated STAT1 activation in vitro. Our findings 
      reveal that upadacitinib can efficiently alleviate alkali-induced corneal 
      inflammation and neovascularization by inhibiting M1 macrophage infiltration. 
      These data demonstrate that upadacitinib is an effective drug for the treatment 
      of corneal alkali burns.
CI  - Copyright (c) 2023. Published by Elsevier B.V.
FAU - Yu, Jianfeng
AU  - Yu J
AD  - Eye Institute, Affiliated Hospital of Nantong University, Nantong 226001, China; 
      Medical School of Nantong University, Nantong 226001, China.
FAU - Shen, Yao
AU  - Shen Y
AD  - Eye Institute, Affiliated Hospital of Nantong University, Nantong 226001, China; 
      Medical School of Nantong University, Nantong 226001, China.
FAU - Luo, Jiawei
AU  - Luo J
AD  - Eye Institute, Affiliated Hospital of Nantong University, Nantong 226001, China; 
      Medical School of Nantong University, Nantong 226001, China.
FAU - Jin, Juan
AU  - Jin J
AD  - Nantong Hospital of Traditional Chinese Medicine, Nantong 226001, China.
FAU - Li, Pengfei
AU  - Li P
AD  - Eye Institute, Affiliated Hospital of Nantong University, Nantong 226001, China; 
      Medical School of Nantong University, Nantong 226001, China.
FAU - Feng, Peida
AU  - Feng P
AD  - Medical School of Nantong University, Nantong 226001, China.
FAU - Guan, Huaijin
AU  - Guan H
AD  - Eye Institute, Affiliated Hospital of Nantong University, Nantong 226001, China; 
      Medical School of Nantong University, Nantong 226001, China. Electronic address: 
      guanhjeye@163.com.
LA  - eng
PT  - Journal Article
DEP - 20230203
PL  - Netherlands
TA  - Int Immunopharmacol
JT  - International immunopharmacology
JID - 100965259
RN  - 0 (Vascular Endothelial Growth Factor A)
RN  - 4RA0KN46E0 (upadacitinib)
RN  - 0 (Alkalies)
SB  - IM
MH  - Mice
MH  - Animals
MH  - *Burns, Chemical/drug therapy/pathology
MH  - Vascular Endothelial Growth Factor A/metabolism
MH  - Alkalies/adverse effects/metabolism
MH  - Cornea
MH  - *Corneal Neovascularization/chemically induced/drug therapy/metabolism
MH  - *Corneal Injuries/metabolism
MH  - Macrophages/metabolism
MH  - *Keratitis/chemically induced/drug therapy
MH  - Inflammation/metabolism
MH  - *Corneal Opacity/complications/metabolism/pathology
MH  - *Eye Burns/chemically induced/drug therapy/pathology
MH  - Disease Models, Animal
OTO - NOTNLM
OT  - Alkali injury
OT  - Corneal inflammation
OT  - Corneal neovascularization
OT  - Macrophage
OT  - Upadacitinib
COIS- Declaration of Competing Interest The authors declare that they have no known 
      competing financial interests or personal relationships that could have appeared 
      to influence the work reported in this paper.
EDAT- 2023/02/06 06:00
MHDA- 2023/03/09 06:00
CRDT- 2023/02/05 18:17
PHST- 2022/09/23 00:00 [received]
PHST- 2022/12/21 00:00 [revised]
PHST- 2022/12/31 00:00 [accepted]
PHST- 2023/02/06 06:00 [pubmed]
PHST- 2023/03/09 06:00 [medline]
PHST- 2023/02/05 18:17 [entrez]
AID - S1567-5769(23)00003-6 [pii]
AID - 10.1016/j.intimp.2023.109680 [doi]
PST - ppublish
SO  - Int Immunopharmacol. 2023 Mar;116:109680. doi: 10.1016/j.intimp.2023.109680. Epub 
      2023 Feb 3.