2022年6月6日
Tryptanthrin attenuates TLR3-mediated STAT1 activation in THP-1 cells
Immunologic Research
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- 巻
- 70
- 号
- 5
- 開始ページ
- 688
- 終了ページ
- 697
- 記述言語
- 英語
- 掲載種別
- 研究論文(学術雑誌)
- DOI
- 10.1007/s12026-022-09301-z
Upon viral infection, dysregulated immune responses are associated with the disease exacerbation and poor prognosis. The Janus kinase/signal transducers and activators of transcription (JAK/STAT) pathway are essential for the innate immune responses against invading viruses as well as for sustained activation of macrophages. Tryptanthrin, a natural alkaloid, exhibits various bioactivities, including anti-microbial and anti-inflammatory effects. The aim of this study was to elucidate the effects of tryptanthrin on toll-like receptor 3 (TLR3)-mediated STAT1 activation in macrophages in vitro. Using phorbol myristate acetate (PMA)-differentiated THP-1 cells, we analyzed the protein level of phosphorylated-STAT1 (p-STAT1) upon stimulation with polyinosinic-polycytidylic acid (poly IC), a well-known TLR3 ligand, with and without tryptanthrin. We found that tryptanthrin decreased the protein level of p-STAT1 in a concentration-dependent manner after poly IC stimulation. On the other hand, tryptanthrin did not affect the levels of p-STAT1 upon stimulation with lipopolysaccharide from Escherichia coli. Consistently, tryptanthrin suppressed poly IC-induced mRNA expression of interferon (IFN)-stimulated genes which are regulated by STAT1. Moreover, tryptanthrin decreased the protein level of phosphorylated-IFN regulatory factor 3 and the subsequent IFN-β mRNA induction after poly IC stimulation. Tryptanthrin is a promising therapeutic agent for the aberrant activation of macrophages caused by viral infection.
- リンク情報
- ID情報
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- DOI : 10.1007/s12026-022-09301-z
- ORCIDのPut Code : 114055150
- PubMed ID : 35666435
- PubMed Central 記事ID : PMC9169444