ArticleCell reports2022
Small-molecule screening identifies Syk kinase inhibition and rutaecarpine as modulators of macrophage training and SARS-CoV-2 infection.
Article in Cell reports, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 7 papers.
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Who cites it
7 citing papers in PubMed, 11 citations in OpenAlex.
- Identifying ICAM-1 as a Therapeutic Target for Cytokine Storm in Human Macrophages Through Integrative Bioinformatics Approaches.Molecules (Basel, Switzerland) · 2026Article
- Sustained monocyte activation by persistent challenges with either oxLDL or free cholesterol and underlying mechanisms.ImmunoHorizons · 2026Article
- Bioengineering approaches to trained immunity: Physiologic targets and therapeutic strategies.eLife · 2025Review
- Adrenal gland macrophages regulate glucocorticoid production through Trem2 and TGF-β.JCI insight · 2024Article
- Evodiamine Alleviates 2,4-Dinitro-1-Chloro-Benzene-Induced Atopic Dermatitis-like Symptoms in BALB/c Mice.Life (Basel, Switzerland) · 2024Article
- Article
- Rutaecarpine ameliorates osteoarthritis by inhibiting PI3K/AKT/NF‑κB and MAPK signalling transduction through integrin αVβ3.International journal of molecular medicine · 2023Article
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Authors and funding
14 authors at 3 institutions in 1 country.
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Abstract
Biologically active small molecules can impart modulatory effects, in some cases providing extended long-term memory. In a screen of biologically active small molecules for regulators of tumor necrosis factor (TNF) induction, we identify several compounds with the ability to induce training effects on human macrophages. Rutaecarpine shows acute and long-term modulation, enhancing lipopolysaccharide (LPS)-induced pro-inflammatory cytokine secretion and relieving LPS tolerance in human macrophages. Rutaecarpine inhibits β-glucan-induced H3K4Me3 marks at the promoters of several pro-inflammatory cytokines, highlighting the potential of this molecule to modulate chromosomal topology. Syk kinase inhibitor (SYKi IV), another screen hit, promotes an enhanced response to LPS similar to that previously reported for β-glucan-induced training. Macrophages trained with SYKi IV show a high degree of resistance to influenza A, multiple variants of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), and OC43 coronavirus infection, highlighting a potential application of this molecule and other SYKis as prophylactic treatments for viral susceptibility.
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