PMID- 29396047
OWN - NLM
STAT- MEDLINE
DCOM- 20190730
LR  - 20211204
IS  - 1096-0023 (Electronic)
IS  - 1043-4666 (Linking)
VI  - 108
DP  - 2018 Aug
TI  - Fisetin inhibits TNF-alpha/NF-kappaB-induced IL-8 expression by targeting PKCdelta in human 
      airway epithelial cells.
PG  - 247-254
LID - S1043-4666(18)30004-8 [pii]
LID - 10.1016/j.cyto.2018.01.004 [doi]
AB  - Fisetin (3,7,3',4'-tetrahydroxyflavone), a natural flavonoid, is a therapeutic 
      agent for respiratory inflammatory diseases such as chronic obstructive pulmonary 
      disease (COPD). However, detailed molecular mechanisms regarding the target 
      protein of fisetin remain unknown. Fisetin significantly reduces tumour necrosis 
      factor alpha (TNF-alpha)-induced interleukin (IL)-8 levels by inhibiting both nuclear 
      factor kappa B (NF-kappaB) transcriptional activity and the phosphorylation of its 
      upstream effectors. We show that fisetin prevents interactions between protein 
      kinase C (PKC)delta and TNF receptor-associated factor 2 (TRAF2), thereby inhibiting 
      the inhibitor of kappa B kinase (IKK)/NF-kappaB downstream signalling cascade. 
      Furthermore, we found that fisetin directly binds to PKCdelta in vitro. Our findings 
      provide evidence that fisetin inhibits the TNF-alpha-activated IKK/NF-kappaB cascade by 
      targeting PKCdelta, thereby mediating inflammatory diseases such as COPD. These data 
      suggest that fisetin is a good therapeutic drug for the treatment of inflammatory 
      lung diseases, such as COPD, by inhibiting the TNF-alpha/NF-kappaB signalling pathway.
CI  - Copyright (c) 2018 Elsevier Ltd. All rights reserved.
FAU - Lee, Seoghyun
AU  - Lee S
AD  - Natural Medicine Research Center, Korea Research Institute of Bioscience and 
      Biotechnology (KRIBB), 30 Yeongudanji-ro, Ochang, Cheongju, Chungbuk 28116, 
      Republic of Korea; College of Bioscience and Biotechnology, Chungnam National 
      University, Daejeon 34134, Republic of Korea.
FAU - Ro, Hyunju
AU  - Ro H
AD  - College of Bioscience and Biotechnology, Chungnam National University, Daejeon 
      34134, Republic of Korea.
FAU - In, Hyun Ju
AU  - In HJ
AD  - Division of Vaccine Research, Korea National Research Institute of Health, Korea 
      Centers for Disease Control and Prevention, Cheongju, Chungbuk 28159, Republic of 
      Korea.
FAU - Choi, Ji-Hee
AU  - Choi JH
AD  - Natural Medicine Research Center, Korea Research Institute of Bioscience and 
      Biotechnology (KRIBB), 30 Yeongudanji-ro, Ochang, Cheongju, Chungbuk 28116, 
      Republic of Korea.
FAU - Kim, Mun-Ock
AU  - Kim MO
AD  - Natural Medicine Research Center, Korea Research Institute of Bioscience and 
      Biotechnology (KRIBB), 30 Yeongudanji-ro, Ochang, Cheongju, Chungbuk 28116, 
      Republic of Korea.
FAU - Lee, Jinhyuk
AU  - Lee J
AD  - Korean Bioinformation Center (KOBIC), Korea Research Institute of Bioscience and 
      Biotechnology, 125 Gwahak-ro, Yuseong, Daejeon 34141, Republic of Korea.
FAU - Hong, Sung-Tae
AU  - Hong ST
AD  - Department of Anatomy & Cell Biology, College of Medicine, Chungnam National 
      University, 266, Munhwa-Ro, Daejeon 35015, Republic of Korea. Electronic address: 
      mogwai@cnu.ac.kr.
FAU - Lee, Su Ui
AU  - Lee SU
AD  - Natural Medicine Research Center, Korea Research Institute of Bioscience and 
      Biotechnology (KRIBB), 30 Yeongudanji-ro, Ochang, Cheongju, Chungbuk 28116, 
      Republic of Korea; Immunotherapy Convergence Research Center, Korea Research 
      Institute of Bioscience and Biotechnology (KRIBB), Yuseong-gu, Daejeon 34141, 
      Republic of Korea. Electronic address: iamsuui@kribb.re.kr.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20180201
PL  - England
TA  - Cytokine
JT  - Cytokine
JID - 9005353
RN  - 0 (CXCL8 protein, human)
RN  - 0 (Flavonoids)
RN  - 0 (Flavonols)
RN  - 0 (Interleukin-8)
RN  - 0 (NF-kappa B)
RN  - 0 (TNF Receptor-Associated Factor 2)
RN  - 0 (Tumor Necrosis Factor-alpha)
RN  - EC 2.7.11.13 (Protein Kinase C-delta)
RN  - OO2ABO9578 (fisetin)
MH  - Epithelial Cells/*drug effects/enzymology
MH  - Flavonoids/*pharmacology
MH  - Flavonols
MH  - HEK293 Cells
MH  - Humans
MH  - Interleukin-8/*metabolism
MH  - Molecular Docking Simulation
MH  - NF-kappa B/*antagonists & inhibitors/metabolism
MH  - Phosphorylation
MH  - Protein Binding
MH  - Protein Kinase C-delta/*metabolism
MH  - *Signal Transduction
MH  - TNF Receptor-Associated Factor 2/metabolism
MH  - Tumor Necrosis Factor-alpha/*metabolism
OTO - NOTNLM
OT  - Chronic obstructive pulmonary disease (COPD)
OT  - Fisetin
OT  - IL-8
OT  - PKCdelta
OT  - TNF-alpha/NF-kappaB pathway
EDAT- 2018/02/06 06:00
MHDA- 2019/07/31 06:00
CRDT- 2018/02/04 06:00
PHST- 2017/10/10 00:00 [received]
PHST- 2018/01/02 00:00 [revised]
PHST- 2018/01/04 00:00 [accepted]
PHST- 2018/02/06 06:00 [pubmed]
PHST- 2019/07/31 06:00 [medline]
PHST- 2018/02/04 06:00 [entrez]
AID - S1043-4666(18)30004-8 [pii]
AID - 10.1016/j.cyto.2018.01.004 [doi]
PST - ppublish
SO  - Cytokine. 2018 Aug;108:247-254. doi: 10.1016/j.cyto.2018.01.004. Epub 2018 Feb 1.