PMID- 35483573
OWN - NLM
STAT- MEDLINE
DCOM- 20230616
LR  - 20230620
IS  - 2320-2890 (Electronic)
IS  - 2319-4170 (Print)
IS  - 2319-4170 (Linking)
VI  - 46
IP  - 2
DP  - 2023 Apr
TI  - Capmatinib suppresses LPS-induced interaction between HUVECs and THP-1 monocytes 
      through suppression of inflammatory responses.
PG  - 100534
LID - S2319-4170(22)00071-3 [pii]
LID - 10.1016/j.bj.2022.04.005 [doi]
LID - 100534
AB  - BACKGROUND: Capmatinib (CAP) is a drug that has been used to treat non-small cell 
      lung cancer (NSCLC) in adults. Presently, its novel effects on skeletal muscle 
      insulin signaling, inflammation, and lipogenesis in adipocytes have been 
      uncovered with a perspective of drug repositioning. However, the impact of CAP on 
      LPS-mediated interaction between human umbilical vein endothelial cells (HUVECs) 
      and THP-1 monocytes has yet to be investigated. METHODS: HUVECs and THP-1 
      monocytes were treated with LPS and CAP. The protein expression levels were 
      determined using Western blotting. Target protein knockdown was conducted using 
      small interfering (si) RNA transfection. Interactions between HUVECs and 
      THP-1 cells were assayed using green fluorescent dye. RESULTS: This study found 
      that CAP treatment ameliorated cell adhesion between THP-1 monocytes and HUVECs 
      and the expression of adhesive molecules, such as intracellular adhesion 
      molecule-1 (ICAM-1), vascular cell adhesion molecule-1 (VCAM-1), and E-selectin. 
      Moreover, phosphorylation of inflammatory markers, such as NFkappaB and IkappaB as well 
      as TNFalpha and monocyte chemoattractant protein-1 (MCP-1) released from HUVECs and 
      THP-1 monocytes, was prevented by CAP treatment. Treatment with CAP augmented 
      PPARdelta and IL-10 expression. siRNA-associated suppression of PPARdelta and IL-10 
      abolished the effects of CAP on cell interaction between HUVECs and THP-1 cells 
      and inflammatory responses. Further, PPARdelta siRNA mitigated CAP-mediated induction 
      of IL-10 expression. CONCLUSION: These findings imply that CAP improves inflamed 
      endothelial-monocyte adhesion via a PPARdelta/IL-10-dependent pathway. The current 
      study provides in vitro evidence for a therapeutic approach for treating 
      atherosclerosis.
CI  - Copyright (c) 2022 Chang Gung University. Published by Elsevier B.V. All rights 
      reserved.
FAU - Park, Hyung Sub
AU  - Park HS
AD  - Department of Surgery, Seoul National University College of Medicine, Seoul, 
      South Korea; Department of Surgery, Seoul National University Bundang Hospital, 
      Seongnam, South Korea.
FAU - Abd El-Aty, A M
AU  - Abd El-Aty AM
AD  - Department of Pharmacology, Faculty of Veterinary Medicine, Cairo University, 
      Giza, Egypt; Department of Medical Pharmacology, Medical Faculty, Ataturk 
      University, Erzurum, Turkey.
FAU - Jeong, Ji Hoon
AU  - Jeong JH
AD  - Department of Pharmacology, College of Medicine, Chung-Ang University, Seoul, 
      Republic of Korea; Department of Global Innovative Drugs, Graduate School of 
      Chung-Ang University, Seoul, Republic of Korea.
FAU - Lee, Taeseung
AU  - Lee T
AD  - Department of Surgery, Seoul National University College of Medicine, Seoul, 
      South Korea; Department of Surgery, Seoul National University Bundang Hospital, 
      Seongnam, South Korea.
FAU - Jung, Tae Woo
AU  - Jung TW
AD  - Department of Pharmacology, College of Medicine, Chung-Ang University, Seoul, 
      Republic of Korea. Electronic address: twjung@cau.ac.kr.
LA  - eng
PT  - Journal Article
DEP - 20220426
PL  - United States
TA  - Biomed J
JT  - Biomedical journal
JID - 101599820
RN  - 130068-27-8 (Interleukin-10)
RN  - 0 (Lipopolysaccharides)
RN  - TY34L4F9OZ (capmatinib)
RN  - 0 (PPAR delta)
RN  - 0 (RNA, Small Interfering)
RN  - 126547-89-5 (Intercellular Adhesion Molecule-1)
SB  - IM
MH  - Humans
MH  - Monocytes/metabolism
MH  - Human Umbilical Vein Endothelial Cells/metabolism
MH  - Interleukin-10
MH  - Lipopolysaccharides/pharmacology/metabolism
MH  - *PPAR delta/metabolism/pharmacology
MH  - *Carcinoma, Non-Small-Cell Lung
MH  - *Lung Neoplasms
MH  - RNA, Small Interfering/metabolism/pharmacology
MH  - Intercellular Adhesion Molecule-1/metabolism/pharmacology
PMC - PMC10267969
OTO - NOTNLM
OT  - Capmatinib
OT  - HUVEC
OT  - IL-10
OT  - Inflammation
OT  - PPAR delta
OT  - THP-1
COIS- Conflicts of interest None.
EDAT- 2022/04/29 06:00
MHDA- 2023/06/16 06:42
PMCR- 2022/04/26
CRDT- 2022/04/28 19:26
PHST- 2021/09/09 00:00 [received]
PHST- 2022/02/09 00:00 [revised]
PHST- 2022/04/20 00:00 [accepted]
PHST- 2023/06/16 06:42 [medline]
PHST- 2022/04/29 06:00 [pubmed]
PHST- 2022/04/28 19:26 [entrez]
PHST- 2022/04/26 00:00 [pmc-release]
AID - S2319-4170(22)00071-3 [pii]
AID - 100534 [pii]
AID - 10.1016/j.bj.2022.04.005 [doi]
PST - ppublish
SO  - Biomed J. 2023 Apr;46(2):100534. doi: 10.1016/j.bj.2022.04.005. Epub 2022 Apr 26.