Yanbo Kou: 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.
Qiyue Jing: 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.
Xiaoqing Yan: Laboratory of Emergency Medicine, Second Clinical Medical College, Xuzhou Medical University, Xuzhou, China.
Junru Chen: 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.
Yusi Shen: 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.
Yulu Ma: 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.
Yaoyao Xiang: 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.
Xiangyang Li: 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.
Xiangye Liu: 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.
Zhuanzhuan Liu: 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.
Yanxia Wei: 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.
Yugang Wang: 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.
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 Q (CoQ) plays a critical role in maintaining intracellular ROS homeostasis and inhibiting excessive Nlrp3 inflammasome activation. However, direct supplementation of CoQ showed unsatisfactory clinical improvement due to its limited absorption and bioavailability. Therefore, stimulating endogenous CoQ biosynthesis by supplementing CoQ precursors may provide a more promising therapeutic approach. In this study, we described the role of 4-hydroxybenzoic acid (4-HBA), a precursor of CoQ, 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 CoQ. 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.
