Itaconic acid, an unsaturated dicarboxylic acid, can be synthesized by prokaryotes and fungi, and is also produced and secreted by aconitate decarboxylase1 (ACOD1, also known as IRG1) in mammalian macrophages during infections[1][2]. It is an endogenous antibacterial metabolite that reduces the production of pro-inflammatory cytokines through various mechanisms[3].
Itaconic acid (10mM, 24h) inhibit S. typhimurium replication in the macrophage[4]. Itaconic acid (4mM, 6-24h) activates autophagy through increased the expression of microtubule-associated protein 1 light chain 3 beta-II (MAP1LC3β-II) in PANC1 cells[5].
Itaconic acid (50mg/kg, once every other day, 2 weeks, i.p.) suppresses tumor growth in human pancreatic cancer cell line PANC1 mouse model[5].
References:
[1] Cordes T, Michelucci A, Hiller K. Itaconic acid: the surprising role of an industrial compound as a mammalian antimicrobial metabolite. Annual review of nutrition. 2015 Jul 17;35(1):451-73.
[2] Wu R, Chen F, Wang N, et al. ACOD1 in immunometabolism and disease. Cellular & molecular immunology. 2020 Aug;17(8):822-33.
[3] Mills EL, Ryan DG, Prag HA, et al. Itaconate is an anti-inflammatory metabolite that activates Nrf2 via alkylation of KEAP1. Nature. 2018 Apr 5;556(7699):113-7.
[4] Zhu X, Guo Y, Liu Z, et al. Itaconic acid exerts anti-inflammatory and antibacterial effects via promoting pentose phosphate pathway to produce ROS. Scientific reports. 2021 Sep 13;11(1):18173.
[5] Qu C, Dai E, Lai T, et al. Itaconic acid induces ferroptosis by activating ferritinophagy. Biochemical and biophysical research communications. 2021 Dec 17;583:56-62.
Itaconic acid是一种不饱和二羧酸，可由原核生物和真菌合成，也可在哺乳动物巨噬细胞感染过程中由乌头酸脱羧酶1（ACOD1，也称为IRG1）产生和分泌[1][2]。它是一种内源性抗菌代谢物，可通过多种机制减少促炎细胞因子的产生[3]。
Itaconic acid（10mM, 24h）可抑制巨噬细胞中的鼠伤寒沙门氏菌复制[4]。Itaconic acid（4mM，6-24h）通过增加PANC1细胞中微管相关蛋白1轻链3β-II（MAP1LC3β-II）的表达来激活自噬[5]。
Itaconic acid（50mg/kg，隔日一次，2周，腹腔注射）可抑制人胰腺癌细胞系PANC1小鼠模型中的肿瘤生长[5]。