Suppression of cytokine response by GATA inhibitor K-7174 via unfolded protein response
| Autor: | James C. Paton, Makiko Yokouchi, Masanori Kitamura, Adrienne W. Paton, Akihiro Shitamura, Tsuyoshi Shimada, Kunihiro Hayakawa, Ayumi Kasai, Nobuhiko Hiramatsu, Yosuke Takano, Maro Okamura, Jian Yao |
|---|---|
| Rok vydání: | 2007 |
| Předmět: |
Protein Denaturation
Protein Folding Thapsigargin Biophysics Anisoles Biology Endoplasmic Reticulum GATA Transcription Factors Biochemistry Cell Line Podocyte Proinflammatory cytokine Mice chemistry.chemical_compound medicine Animals Molecular Biology Dose-Response Relationship Drug Podocytes Endoplasmic reticulum Azepines Cell Biology Tunicamycin Molecular biology Nitric oxide synthase medicine.anatomical_structure chemistry biology.protein Unfolded protein response Cytokines GATA transcription factor |
| Zdroj: | Biochemical and Biophysical Research Communications. 360:470-475 |
| ISSN: | 0006-291X |
| DOI: | 10.1016/j.bbrc.2007.06.082 |
| Popis: | K-7174, a GATA-specific inhibitor, is a putative anti-inflammatory agent that attenuates effects of inflammatory cytokines in certain cell types. However, molecular mechanisms involved have not been elucidated. We found that, in glomerular podocytes, induction of monocyte chemoattractant protein 1 (MCP-1) and inducible nitric oxide synthase (iNOS) by TNF-alpha was abrogated by K-7174. It was correlated with unexpected induction of unfolded protein response (UPR) evidenced by: (1) induction of endogenous indicators 78 kDa glucose-regulated protein and CCAAT/enhancer-binding protein-homologous protein, and (2) suppression of an exogenous indicator, endoplasmic reticulum stress-repressive alkaline phosphatase. In podocytes, induction of UPR by either tunicamycin, thapsigargin, A23187 or AB5 subtilase cytotoxin completely reproduced the suppressive effect of K-7174. Furthermore, K-7174-elicited UPR abrogated induction of MCP-1 and iNOS not only by TNF-alpha but also by medium conditioned by activated macrophages. These results suggested a novel, UPR-dependent mechanism underlying the anti-inflammatory potential of K-7174. |
| Databáze: | OpenAIRE |
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