PMID- 30626802
OWN - NLM
STAT- MEDLINE
DCOM- 20190703
LR  - 20190703
IS  - 1347-5215 (Electronic)
IS  - 0918-6158 (Linking)
VI  - 42
IP  - 3
DP  - 2019 Mar 1
TI  - Curcumin Down-Regulates Toll-Like Receptor-2 Gene Expression and Function in 
      Human Cystic Fibrosis Bronchial Epithelial Cells.
PG  - 489-495
LID - 10.1248/bpb.b18-00928 [doi]
AB  - Cystic fibrosis (CF), the most common lethal inherited disorder caused by 
      mutation in the gene encoding the CF transmembrane regulator (CFTR), is 
      characterized by chronic inflammation that ultimately leads to death from 
      respiratory failure. In CF patients, up-regulation of toll-like receptor-2 
      (TLR2), a pattern recognition receptor that senses CF-pathogenic bacteria 
      Staphylococcus aureus peptidoglycan (PGN), in airway epithelial cells is 
      observed, and enhanced proinflammatory responses towards PGN may result in 
      detrimental effects in CF patients. Here, we showed that curcumin, a well known 
      anti-inflammatory agent derived from the curry spice turmeric, inhibits TLR2 
      expression in CF bronchial epithelial cell line, CFBE41o- cells. Strong 
      suppression of TLR2 gene and protein expression was observed at more than 40 microM 
      of curcumin treatment in CFBE41o- cells. Consistent with decreased expression of 
      TLR2, PGN-dependent interleukin-8 (IL-8) gene up-regulation was markedly reduced 
      by 40 microM of curcumin treatment. Strong reductions of TLR2 gene expression and 
      function were also observed in primary human CF bronchial epithelial cells, but 
      not in human non-CF primary cells. Interestingly, curcumin treatment decreased 
      nuclear expression of transcription factor specificity protein 1 (SP1), a factor 
      that is critical for increased basal TLR2 expression in CF cell line and primary 
      cells. Finally, curcumin-dependent SP1 reduction was diminished by anti-oxidant 
      N-acetylcystein (NAC) and proteasomal inhibitor MG-132, suggesting the crucial 
      roles of oxidative and proteasomal degradation pathways. Taken together, our 
      study shows that curcumin down-regulates TLR2 gene expression and function in CF 
      bronchial epithelial cells possibly by accelerating SP1 degradation via an 
      oxidative process.
FAU - Chaudhary, Niraj
AU  - Chaudhary N
AD  - Department of Molecular Medicine, Graduate School of Pharmaceutical Sciences, 
      Kumamoto University.
AD  - Program for Leading Graduate School of "HIGO (Health Life Science: 
      Interdisciplinary and Global Oriented) Program," Kumamoto University.
FAU - Ueno-Shuto, Keiko
AU  - Ueno-Shuto K
AD  - Laboratory of Pharmacology, Division of Life Science, Faculty of Pharmaceutical 
      Sciences, Sojo University.
FAU - Ono, Tomomi
AU  - Ono T
AD  - Department of Molecular Medicine, Graduate School of Pharmaceutical Sciences, 
      Kumamoto University.
FAU - Ohira, Yuko
AU  - Ohira Y
AD  - Department of Molecular Medicine, Graduate School of Pharmaceutical Sciences, 
      Kumamoto University.
FAU - Watanabe, Kenji
AU  - Watanabe K
AD  - Institute of Gene Research, Yamaguchi University Science Research Center.
FAU - Nasu, Aoi
AU  - Nasu A
AD  - Department of Molecular Medicine, Graduate School of Pharmaceutical Sciences, 
      Kumamoto University.
FAU - Fujikawa, Haruka
AU  - Fujikawa H
AD  - Department of Molecular Medicine, Graduate School of Pharmaceutical Sciences, 
      Kumamoto University.
AD  - Program for Leading Graduate School of "HIGO (Health Life Science: 
      Interdisciplinary and Global Oriented) Program," Kumamoto University.
FAU - Nakashima, Ryunosuke
AU  - Nakashima R
AD  - Department of Molecular Medicine, Graduate School of Pharmaceutical Sciences, 
      Kumamoto University.
FAU - Takahashi, Noriki
AU  - Takahashi N
AD  - Department of Molecular Medicine, Graduate School of Pharmaceutical Sciences, 
      Kumamoto University.
FAU - Suico, Mary Ann
AU  - Suico MA
AD  - Department of Molecular Medicine, Graduate School of Pharmaceutical Sciences, 
      Kumamoto University.
FAU - Kai, Hirofumi
AU  - Kai H
AD  - Department of Molecular Medicine, Graduate School of Pharmaceutical Sciences, 
      Kumamoto University.
FAU - Shuto, Tsuyoshi
AU  - Shuto T
AD  - Department of Molecular Medicine, Graduate School of Pharmaceutical Sciences, 
      Kumamoto University.
LA  - eng
PT  - Journal Article
DEP - 20190110
PL  - Japan
TA  - Biol Pharm Bull
JT  - Biological & pharmaceutical bulletin
JID - 9311984
RN  - 0 (Enzyme Inhibitors)
RN  - 0 (TLR2 protein, human)
RN  - 0 (Toll-Like Receptor 2)
RN  - EC 3.4.25.1 (Proteasome Endopeptidase Complex)
RN  - IT942ZTH98 (Curcumin)
SB  - IM
MH  - Bronchi/*cytology
MH  - Cell Line
MH  - Curcumin/*pharmacology
MH  - Cystic Fibrosis
MH  - Down-Regulation/drug effects
MH  - Enzyme Inhibitors/pharmacology
MH  - Epithelial Cells/*drug effects
MH  - Gene Expression Regulation/*drug effects
MH  - Humans
MH  - Oxidation-Reduction
MH  - Proteasome Endopeptidase Complex
MH  - Toll-Like Receptor 2/genetics/*metabolism
OTO - NOTNLM
OT  - bronchial epithelial cell
OT  - curcumin
OT  - cystic fibrosis
OT  - specificity protein 1 (SP1)
OT  - toll-like receptor-2
EDAT- 2019/01/11 06:00
MHDA- 2019/07/04 06:00
CRDT- 2019/01/11 06:00
PHST- 2019/01/11 06:00 [pubmed]
PHST- 2019/07/04 06:00 [medline]
PHST- 2019/01/11 06:00 [entrez]
AID - 10.1248/bpb.b18-00928 [doi]
PST - ppublish
SO  - Biol Pharm Bull. 2019 Mar 1;42(3):489-495. doi: 10.1248/bpb.b18-00928. Epub 2019 
      Jan 10.