2. Academic Validation
  3. 4-Hydroxybenzoic acid restrains Nlrp3 inflammasome priming and activation via disrupting PU.1 DNA binding activity and direct antioxidation

4-Hydroxybenzoic acid restrains Nlrp3 inflammasome priming and activation via disrupting PU.1 DNA binding activity and direct antioxidation

  • Chem Biol Interact. 2024 Dec 1:404:111262. doi: 10.1016/j.cbi.2024.111262.
Yanbo Kou 1,  Qiyue Jing 1,  Xiaoqing Yan 2,  Junru Chen 1,  Yusi Shen 1,  Yulu Ma 1,  Yaoyao Xiang 1,  Xiangyang Li 1,  Xiangye Liu 1,  Zhuanzhuan Liu 1,  Yanxia Wei 1,  Yugang Wang 3
Affiliations

Affiliations

  • 1 Laboratory of Infection and Immunity, Jiangsu Key Laboratory of Immunity and Metabolism, Department of Pathogenic Biology and Immunology, School of Basic Medicine, Xuzhou Medical University, Xuzhou, China; Jiangsu International Laboratory of Immunity and Metabolism, China.
  • 2 Laboratory of Emergency Medicine, Second Clinical Medical College, Xuzhou Medical University, Xuzhou, China.
  • 3 Laboratory of Infection and Immunity, Jiangsu Key Laboratory of Immunity and Metabolism, Department of Pathogenic Biology and Immunology, School of Basic Medicine, Xuzhou Medical University, Xuzhou, China; Jiangsu International Laboratory of Immunity and Metabolism, China. Electronic address: wangyg@xzhmu.edu.cn.
PMID: 39389441 DOI: 10.1016/j.cbi.2024.111262
Abstract

Reactive Oxygen Species (ROS) production is considered central to triggering the nucleotide-binding domain-like receptor family pyrin domain containing 3 (NLRP3) inflammasome activation and the subsequent inflammatory responses. Coenzyme Q10 (CoQ10) plays a critical role in maintaining intracellular ROS homeostasis and inhibiting excessive NLRP3 inflammasome activation. However, direct supplementation of CoQ10 showed unsatisfactory clinical improvement due to its limited absorption and bioavailability. Therefore, stimulating endogenous CoQ10 biosynthesis by supplementing CoQ10 precursors may provide a more promising therapeutic approach. In this study, we described the role of 4-hydroxybenzoic acid (4-HBA), a precursor of CoQ10, in attenuating excessive inflammatory responses. We found that while supplementation of 4-HBA inhibited the priming and activation of NLRP3 inflammasome, this effect was independent of its metabolic transformation into CoQ10. 4-HBA itself exhibits antioxidative activities. Furthermore, 4-HBA can disrupt the binding activity of PU.1 on the promoters of TLR4 and Md2, thereby directly suppressing NLRP3 inflammasome priming during LPS-induced inflammatory responses. Therefore, strategically utilizing 4-HBA or increasing 4-HBA intake may represent a potential strategy for reducing excessive inflammation.

Keywords

4-HBA; Antioxidation; Inflammation; Macrophage; Nlrp3 inflammasome; PU.1.

Figures
Products