Curcumin Down-Regulates Toll-Like Receptor-2 Gene Expression and Function in Human Cystic Fibrosis Bronchial Epithelial Cells
| Autor: | Haruka Fujikawa, Yuko Ohira, Niraj Chaudhary, Keiko Ueno-Shuto, Noriki Takahashi, Mary Ann Suico, Hirofumi Kai, Aoi Nasu, Ryunosuke Nakashima, Kenji Watanabe, Tomomi Ono, Tsuyoshi Shuto |
|---|---|
| Rok vydání: | 2019 |
| Předmět: |
0301 basic medicine
Proteasome Endopeptidase Complex Curcumin Cystic Fibrosis Down-Regulation Pharmaceutical Science Bronchi Inflammation Cell Line Proinflammatory cytokine 03 medical and health sciences chemistry.chemical_compound 0302 clinical medicine Gene expression medicine Humans Enzyme Inhibitors Transcription factor Pharmacology Toll-like receptor Chemistry Epithelial Cells General Medicine Molecular biology Toll-Like Receptor 2 TLR2 030104 developmental biology Gene Expression Regulation Cell culture 030220 oncology & carcinogenesis medicine.symptom Oxidation-Reduction |
| Zdroj: | Biological and Pharmaceutical Bulletin. 42:489-495 |
| ISSN: | 1347-5215 0918-6158 |
| Popis: | 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 µM 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 µM 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. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|