Ahn Huijeong, Lee Hansae, Lee Gilyoung, Park Jeongho, Sung Haan-Woo, Lee Eunsong, Lee Geun-Shik
College of Veterinary Medicine and Institute of Veterinary Science, Kangwon National University, Chuncheon, Gangwon 24341, Republic of Korea.
College of Veterinary Medicine and Institute of Veterinary Science, Kangwon National University, Chuncheon, Gangwon 24341, Republic of Korea.
Int Immunopharmacol. 2021 Dec;101(Pt A):108196. doi: 10.1016/j.intimp.2021.108196. Epub 2021 Sep 30.
Parabens are synthetic chemicals widely used as preservatives in cosmetics, pharmaceuticals, and foods. Although parabens, i.e., ethyl- and methyl-parabens, are considered relatively safe, study of possible health hazards has been undertaken due to the frequent exposure to parabens and their accumulation in the body. In this study, we elucidated the effect of parabens on inflammasome induction of inflammatory responses in innate immunity, such as interleukin (IL)-1β maturation and gasdermin D (GSDMD)-mediating pyroptosis. Parabens attenuated the inflammatory responses to intracellular lipopolysaccharide (LPS) triggering of non-canonical (NC) inflammasome activation, but did not alter canonical inflammasome (i.e., NLRP3, NLRC4 and AIM2) responses. The NC inflammasome is assembled by the interaction of murine caspase (Casp)-11 (Casp4/5 in human) with cytosolic LPS, inducing endotoxin sepsis. Parabens selectively inhibited NC inflammasome activation in both human and murine macrophages and diminished the peritoneal IL-1β production in LPS-injected mice. Parabens blocked the cleavage of GSDMD, Casp1, and Casp4, but did not change the expression of Casp11 or the activity of Casp1. Taken together, the results indicate that parabens could disrupt Gram-negative pathogen infection through the inhibition of NC inflammasome activation.
对羟基苯甲酸酯是一种合成化学物质，广泛用作化妆品、药品和食品中的防腐剂。尽管对羟基苯甲酸酯，即对羟基苯甲酸乙酯和甲酯，被认为相对安全，但由于人们频繁接触对羟基苯甲酸酯及其在体内的积累，因此已对其可能的健康危害展开研究。在本研究中，我们阐明了对羟基苯甲酸酯对先天免疫中炎性小体诱导炎症反应的影响，如白细胞介素（IL）-1β成熟和gasdermin D（GSDMD）介导的细胞焦亡。对羟基苯甲酸酯减弱了细胞内脂多糖（LPS）触发非经典（NC）炎性小体激活所引发的炎症反应，但未改变经典炎性小体（即NLRP3、NLRC4和AIM2）的反应。NC炎性小体由小鼠半胱天冬酶（Casp）-11（人类中的Casp4/5）与胞质LPS相互作用组装而成，可诱导内毒素血症。对羟基苯甲酸酯在人和小鼠巨噬细胞中均选择性抑制NC炎性小体激活，并减少LPS注射小鼠腹腔内IL-1β的产生。对羟基苯甲酸酯可阻断GSDMD、Casp1和Casp4的裂解，但不改变Casp11的表达或Casp1的活性。综上所述，结果表明对羟基苯甲酸酯可通过抑制NC炎性小体激活来干扰革兰氏阴性病原体感染。
