Table 2.
The participation mechanisms of itaconate in different diseases.
| Diseases | Animals and cell | Agents and methods | Main mechanisms | References | |
|---|---|---|---|---|---|
| Anti-inflammation | Sepsis | C57(B6) mice BMDMs(mouse) PBMCs(human) RAW264.7 macrophages |
LPS (Sigma; 2.5 mg/kg;100 ng/ml) OI (Sigma, 50 mg/kg, 125 μM) |
Keap1/Nrf2-IFN | Mills et al., 2018 |
| BMDMs(mouse) C57(B/6J)mice |
LPS (Sigma, 0.1 μg/mouse; 100 ng/mL) D-galactosamine (0.5 mg/g,0.5 mg/g) 4-OI (50 mg/kg; 200 μM) |
Nrf2- HO-1/NQO-1 | Zhang et al., 2021 | ||
| Whole blood (sepsis patients) C57(B/6J) mice Primary peritoneal macrophages RAW264.7 macrophages THP-1 cells(human) |
LPS (Sigma,100 ng/mL; 1 μg/ml) | Itaconate induce immunoparalysis β-glucan reverse immunoparalysis made by itaconate | Li et al., 2013; Dominguez-Andres et al., 2019; Mainali et al., 2021 | ||
| CAPS | C57(B/6J) mice PBMCs, monocytes human HEK293T Cells |
LPS (200 ng/mL) 4-OI (50 mg/kg) |
NLRP3- IL-1β | Hooftman et al., 2020 | |
| PM-Pulmonary inflammation | C57(B/6N,6J)mice BMDMs(mouse) |
LPS (Santa;100 ng/ml) Itaconate (sigma;10 mM) 4-OI (sigma;0.25 mM) |
ACOD1-SDH inhibition | Sun et al., 2020 | |
| IPF | C57(B6)mice primary AMs, HLFs(human) HBEs(human) |
Itaconate (Sigma, 0.25 mg/kg) | ACOD1-antifibrotic | Ogger et al., 2020 | |
| Immunomodulatory | SLE | THP-1 macrophages(human) PBMCs(human) |
LPS (Sigma; 500 ng/mL) 4-OI (25 μM, 2 h) |
Keap1-Nrf2-NF-κB | Tang et al., 2018 |
| Psoriasis | BMDMs(mouse) C57(B6,B/6N,6J) mice BV2 microglial cell |
LPS (Sigma; 100 ng/mL) DI (Sigma; 20 mg/mouse, 250 μM) DMF (Sigma, 50 μM) |
DI-IκBζ- IL-17 | Bambouskova et al., 2018 | |
| Multiple sclerosis | C57(B6),SJL/J mice Microglia(mice) Mononuclear cell(mice) |
LPS (Sigma; 100 ng/mL) DMI (Sigma;400 mg/kg, 150 μM) |
MMP3, MMP9 inhibition inhibite Th1/Th17 differentiation and infiltration to CNS | Kuo et al., 2020 | |
| SAVI | THP-1 cells, PBMCs,HaCat HEK293T, A549 cells(human) | 4-OI (Aarhus University;125 μM, 200 μM) | Nrf2-STING-IFN | Olagnier et al., 2018 | |
| Anti-oxidation | Heart | C57(B6, B/6N) mice BMDM (mouse) RAW264.7 macrophages |
LPS (Sigma; 100 ng/mL) DI (4 mg/kg/min;0.25 mM) |
SDH inhibition HIF-1α/IL-1β, IL-18 reduction not TNF-α production |
Lampropoulou et al., 2016 |
| Brain | C57(B/6J) mice Primary cortical neurons, astrocytes(SD rat) |
Itaconate (15 mg/kg/min) | SDH inhibition ROS/RNS reduction |
Cordes et al., 2020 | |
| C57(B6) mice | DMI (Sigma, 20 mg) | Inhibited toxic conversion of microglia | Zhang et al., 2019 | ||
| Liver | C57 (B/6N, B/6J) mice hepatocytes(human,mouse) NPCs(mouse) |
4-OI (25 mg/kg, 62.5/125 μM) | IRG1-Nrf2- antioxidant | RajanBabu et al., 1999 | |
| Kidney | SD Rat HK-2 cell |
4-OI (1, 10 mg/kg; 1, 10, 30,1 00 μmol/L) | 4-OI-TGF-β/Smad- NF-κB | Tang et al., 2019 | |
| Bone | C57(B6)mice BMMs(mouse) OB-6 (human) |
LPS (Sigma;10 ng/ml) DI (Sigma,10 μM) 4-OI (MedChemExpress, 50 mg/kg) |
Nrf2—Hrd1- ubiquitination pathway | Sun et al., 2019; Zheng et al., 2020 | |
| Cancer | CAC | C57(B6)mice | DI (10 mg/kg) | Inhibited IL-1β/CCL2 and MDSC Infiltration reduced CAC risk | Wang et al., 2020 |
| Peritoneal tumors | C57(B6)mice Peritoneal Mφ(mouse) B16 melanoma, 3LL, and MC38 PBL(human) |
/ | Irg1-ROS-MAPK(promote cancer) | Weiss et al., 2018 | |
| Anti-bacterial | Tuberculosis Yersinia pestis Pseudomonas aeruginosa et al. |
C57(B6,B/6N)mice SJL (CD45.1) mice |
Itaconate (Sigma, 0.25 mM) | Irg1/NF-κB B12-dependent MCM inhibition ICL inhibition |
Nair et al., 2018; Ruetz et al., 2019; Wang et al., 2019 |
| Antivirus | COVID-19 SARS-CoV2 HSV-1 HSV-2 VACV ZIKV |
C57 (B/6N, B/6J) mouse Primary cell (human, mouse) PBMCs(human) |
4-OI (125 μM, 150 μM) | IRG1- RIPK3 SDH inhibition NRF2- IRF3 |
Dalglish, 2020; Olagnier et al., 2020; Song J. W. et al., 2020; Zhao et al., 2020 |
This table summarizes literary papers focusing on the experimental evidence from animal studies (i.e., experimental model and methods, agent dosage, and mechanisms).