Hydroxy-Safflower Yellow A inhibits the TNFR1-Mediated Classical Pathway by Inducing Shedding of TNFR1

Haifang Wang, Jinlian Liu, Yuejin Yang, Qingwen Cao, Xueping Huo, Shuhui Ma, Jun Hu, Fredrick Pavalko, Qinshe Liu

Research output: Contribution to journalArticle

3 Citations (Scopus)

Abstract

Hydroxy-safflower yellow A (HSYA) is the major active component of safflower, a traditional Asia herbal medicine well known for its cardiovascular protective activities. The purpose of this study was to investigate the effect of HSYA on TNF-α-induced inflammatory responses in arterial endothelial cells (AECs) and to explore the mechanisms involved. The results showed that HSYA suppressed the up-regulation of ICAM-1 expression in TNF-α-stimulated AECs in a dose-dependent manner. High concentration (120μM) HSYA significantly inhibited the TNF-α-induced adhesion of RAW264.7 cells to AECs. HSYA blocked the TNFR1-mediated phosphorylation and degradation of IκBα and also prevented the nuclear translocation of NF-κB p65. Moreover, HSYA reduced the cell surface level of TNFR1 and increased the content of sTNFR1 in the culture media. TNF-α processing inhibitor-0 (TAPI-0) prevented the HSYA inhibition of TNFR1-induced IκBα degradation, implying the occurrence of TNFR1 shedding. Furthermore, HSYA induced phosphorylation of TNF-α converting enzyme (TACE) at threonine 735, which is thought to be required for its activation. Conclusively, HSYA suppressed TNF-α-induced inflammatory responses in AECs, at least in part by inhibiting the TNFR1-mediated classical NF-κB pathway. TACE-mediated TNFR1 shedding can be involved in this effect. Our study provides new evidence for the antiinflammatory and anti-atherosclerotic effects of HSYA.

Original languageEnglish (US)
JournalPhytotherapy Research
DOIs
StateAccepted/In press - 2016

Fingerprint

Receptors, Tumor Necrosis Factor, Type I
Endothelial Cells
Phosphorylation
Carthamus tinctorius
safflower yellow
Herbal Medicine
Intercellular Adhesion Molecule-1
Threonine
Cell Adhesion
Culture Media
Anti-Inflammatory Agents
Up-Regulation

Keywords

  • Arterial endothelial cell
  • Hydroxy-safflower yellow A
  • NF-κB pathway
  • TNF-α
  • TNF-α converting enzyme
  • TNFR1

ASJC Scopus subject areas

  • Pharmacology

Cite this

Hydroxy-Safflower Yellow A inhibits the TNFR1-Mediated Classical Pathway by Inducing Shedding of TNFR1. / Wang, Haifang; Liu, Jinlian; Yang, Yuejin; Cao, Qingwen; Huo, Xueping; Ma, Shuhui; Hu, Jun; Pavalko, Fredrick; Liu, Qinshe.

In: Phytotherapy Research, 2016.

Research output: Contribution to journalArticle

Wang, Haifang ; Liu, Jinlian ; Yang, Yuejin ; Cao, Qingwen ; Huo, Xueping ; Ma, Shuhui ; Hu, Jun ; Pavalko, Fredrick ; Liu, Qinshe. / Hydroxy-Safflower Yellow A inhibits the TNFR1-Mediated Classical Pathway by Inducing Shedding of TNFR1. In: Phytotherapy Research. 2016.
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AU - Wang, Haifang

AU - Liu, Jinlian

AU - Yang, Yuejin

AU - Cao, Qingwen

AU - Huo, Xueping

AU - Ma, Shuhui

AU - Hu, Jun

AU - Pavalko, Fredrick

AU - Liu, Qinshe

PY - 2016

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AB - Hydroxy-safflower yellow A (HSYA) is the major active component of safflower, a traditional Asia herbal medicine well known for its cardiovascular protective activities. The purpose of this study was to investigate the effect of HSYA on TNF-α-induced inflammatory responses in arterial endothelial cells (AECs) and to explore the mechanisms involved. The results showed that HSYA suppressed the up-regulation of ICAM-1 expression in TNF-α-stimulated AECs in a dose-dependent manner. High concentration (120μM) HSYA significantly inhibited the TNF-α-induced adhesion of RAW264.7 cells to AECs. HSYA blocked the TNFR1-mediated phosphorylation and degradation of IκBα and also prevented the nuclear translocation of NF-κB p65. Moreover, HSYA reduced the cell surface level of TNFR1 and increased the content of sTNFR1 in the culture media. TNF-α processing inhibitor-0 (TAPI-0) prevented the HSYA inhibition of TNFR1-induced IκBα degradation, implying the occurrence of TNFR1 shedding. Furthermore, HSYA induced phosphorylation of TNF-α converting enzyme (TACE) at threonine 735, which is thought to be required for its activation. Conclusively, HSYA suppressed TNF-α-induced inflammatory responses in AECs, at least in part by inhibiting the TNFR1-mediated classical NF-κB pathway. TACE-mediated TNFR1 shedding can be involved in this effect. Our study provides new evidence for the antiinflammatory and anti-atherosclerotic effects of HSYA.

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