Table 1B.
Trained-immunity-regulating pathway inhibitors.
| 1st stimulus | 2nd stimulus | Inhibitor | Function | Effect on trained immunity | PMID |
|---|---|---|---|---|---|
| I- Inhibition of signaling pathways | |||||
| β-glucan (10 μg/ml) for 24 h | LPS (10 ng/ml) Pam3Cys (10 g/ml) |
Wortmannin | Akt inhibitor | Inhibit trained immunity | 25258083 |
| β-glucan (10 μg/ml) for 24 h | LPS (10 ng/ml) Pam3Cys (10 g/ml) |
Rapamycin | mTOR inhibitor | Inhibit trained immunity | 25258083 |
| β-glucan (10 μg/ml) for 24 h | LPS (10 ng/ml) Pam3Cys (10 g/ml) |
AICAR | mTOR inhibitor | Inhibits trained immunity | 25258083 |
| β-glucan (10 μg/ml for 24 h | LPS (10 ng/ml) Pam3Cys (10 g/ml) |
Metformin | AMPK inhibition | Inhibit trained immunity | 25258083 |
| β-glucan (10 μg/ml) for 24 h | LPS (10 ng/ml) Pam3Cys (10 g/ml) |
Ascorbate | HIF1α inhibitor | Inhibit trained immunity | 25258083 |
| LPS (200 ng/ml) for 6 h | OxLDL (50 μg/mL) for 24 h | Z-VAD-fmk | NLRP3 activation inhibitor | Inhibits IL-1β secretion | 23812099 |
| LPS (200 ng/ml) for 6h | OxLDL (50 μg/mL) for 24 h | MβCD | Cholesterol crystal formation inhibitor | inhibits the cholesterol crystals and IL-1β secretion | 23812099 |
| II- Inhibition of metabolic pathways | |||||
| β-glucan (10 μg/ml) for 24 h | LPS (10ng/ml) Pam3Cys (10 g/ml) |
2-DG | Inhibits HK2 (glycolytic rate limiting step) | Inhibit trained immunity | 27926861 25258083 |
| OxLDL (10 μg/mL) for 24 h | LPS (10 ng/ml) | 3PO | Inhibit glycolytic enzyme PFKFB3 | Inhibit trained immunity | 32350546 |
| β-glucan (5 μg/ml), oxLDL (10 μg/ml), (R)-mevalonic acid (100–1000 μM), BCG (5 μg/ml) | LPS (10 ng/ml) Pam3Cys (10 μg/ml) |
fluvastatin | HMGCAR inhibitor | Inhibit trained immunity | 29328908 |
| β-glucan (5 μg/ml), oxLDL (10 μg/ml), (R)-mevalonic acid (100–1000 μM), BCG (5 μg/ml) |
LPS (10 ng/ml) Pam3Cys (10 μg/ml) |
6-fluoromeval-onate | Mevalonate-pyrophosphate decarboxylase inhibitor | Enhance trained immunity | 29328908 |
| LPS (200 ng/ml) for 6 h | OxLDL (50 μg/mL) for 24 h | CYTOD | CD36 inhibitor | inhibit formation of cholesterol crystals and IL-1β secretion | 23812099 |
| Aldosterone for 24 h | LPS (10 ng/ml) Pam3Cys (10 μg/ml) |
Cerulenin | FAS inhibitor | Inhibit trained immunity | 31119285 32241223 |
| III- Inhibition of epigenetic reprogramming | |||||
| β-glucan (10 μg/ml) for 24 h | LPS (10 ng/ml) Pam3Cys (10 g/ml) |
MTA | Non-selective Methyltransferase inhibitor | Inhibit trained immunity | 25258083 29328908 30380404 |
| β-glucan (10 μg/ml) for 24 h | LPS (10 ng/ml) Pam3Cys (10 g/ml) |
ITF (ITF2357) | HDACi | Inhibit trained immunity | 25258083 |
| β-glucan (10 μg/ml) for 24 h | LPS (10 ng/ml) Pam3Cys (10 g/ml) |
Cyproheptadine | Set7 methyltransferase inhibitor | Inhibit glycolysis | 25258083 |
| β-glucan (10 μg/ml) for 24 h | LPS (10 ng/ml) Pam3Cys (10 g/ml) |
Resveratrol | HDAC/sirtuins activator | Inhibit trained immunity | 25258083 30380404 |
| - | - | UMLILO | Inhibit H3K4me3 epigenetic priming | Inhibit trained immunity | 30733945 |
Abbreviation: 2-DG: 2-deoxyglucose, HK2: Hexokinase2, PFKFB3: Phosphofractokinase-2/FBPase isozyme 6-phosphofructo-2-kinase/fructose-2,6-biphosphatase 3, HMGCAR: 3-hydroxy-3-methylglutaryl CoA reductase, IL1-β: Interleukin 1-β, HDACi: Histone deacetylase inhibitor, AICAR: Adenosine monophosphate–activated protein kinase (AMPK) activator, Z-VAD-fmk: Benzyloxycarbonyl-Val-Ala-Asp-fluoromethyl ketone, MβCD: Methyl-β-cyclodextrin, 3PO: 3-(3-pyridinyl)-1-(4-pyridinyl)-2-propen-1-one, CYTOD: Cytochalasin D, FAS: Fatty acid synthetase, MTA: 5′-Methylthioadenosine, UMLILO: Upstream Master LncRNA of the inflammatory chemokine Locus.