The inhibitory effect of DIF-3 on polyinosinic–polycytidylic acid-induced innate immunity activation in human cerebral microvascular endothelial cells

Ryusei Araya, Shihu Men, Yoshinori Uekusa, Zaiqiang Yu, Haruhisa Kikuchi, Kazuyuki Daitoku, Masahito Minakawa, Shogo Kawaguchi, Ken Ichi Furukawa, Yoshiteru Oshima, Tadaatsu Imaizumi, Kazuhiko Seya

研究成果: Article査読

抄録

For the treatment and prevention of autoinflammatory diseases, it is essential to develop the drug, regulating the innate immune system. Although differentiation-inducing factor (DIF) derivatives, extracted from the cellular slime mold, Dictyostelium discoideum, exhibit immunomodulatory effects, their effects on the regulation of innate immunity in brain are unknown. In this study, we used the human cerebral microvascular endothelial cell line, hCMEC/D3, to investigate the effects of DIF derivatives on the generation of C-X-C motif chemokine (CXCL) 10 and interferon (IFN)-β induced by polyinosinic–polycytidylic acid (poly IC). DIF-3 (1–10 μM), but not DIF-1 and DIF-2, dose-dependently inhibited the biosynthesis of not only CXCL10 but also CXCL16 and C–C motif chemokine 2 induced by poly IC. DIF-3 also strongly decreased IFN-β mRNA expression and protein release from the cells induced by poly IC through the prohibition of p65, a subtype of NF-ĸB, not interferon regulatory transcription factor 3 phosphorylation. In the docking simulation study, we confirmed that DIF-3 had a high affinity to p65. These results suggest that DIF-3 regulates the innate immune system by inhibiting TLR3/IFN-β signaling axis through the NF-ĸB phosphorylation inhibition.

本文言語English
ページ(範囲)157-165
ページ数9
ジャーナルJournal of Pharmacological Sciences
154
3
DOI
出版ステータスPublished - 2024 3月

ASJC Scopus subject areas

  • 分子医療
  • 薬理学

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