文献类型：期刊文献

英文题名：Formaldehyde aggravates allergic contact dermatitis by facilitating NLRP3 inflammasome activation in macrophages

作者：Ma, Huijuan[1];Shu, Qi[1];Li, Zhiming[1];Song, Xiaodong[2];Xu, Huan[1]

机构：[1]East China Univ Sci & Technol, Sch Pharm, Shanghai Frontiers Sci Ctr Optogenet Tech Cell Met, Shanghai Key Lab New Drug Design, Shanghai 200237, Peoples R China;[2]Fudan Univ, Hua Shan Hosp North, Med Lab Dept, Shanghai 201907, Peoples R China

年份：2023

卷号：117

外文期刊名：INTERNATIONAL IMMUNOPHARMACOLOGY

收录：;WOS:【SCI-EXPANDED(收录号:WOS:000948458100001)】；

基金：This work was funded by National Natural Science Foundation of China [grant No. 42177417 and 21906057to H. X.] . This work was also funded by Shanghai Frontiers Science Center of Optogenetic Techniques for Cell Metabolism (Shanghai Municipal Education Commission) .

语种：英文

外文关键词：NLRP3 inflammasome; Formaldehyde immunotoxicity; Allergic contact dermatitis; Inflammatory cytokines; Caspase-1; Macrophages

摘要：Formaldehyde (FA) is known to be an environmental pollutant and contact sensitizer at 1 % or 2 % concentrations, which can induce inflammatory diseases such as allergic contact dermatitis (ACD). However, the aggravative effects of FA on ACD at legitimate low concentrations in cosmetics have not been studied. The activation of NOD-, LRR- and pyrin domain-containing protein 3 (NLRP3) inflammasome in ACD was recently identified, and the inflammatory responses were attenuated by NLRP3 inhibition. Since non-cytotoxic concentrations of FA at 50 and 100 mu M were found to reinforce inflammatory responses in macrophages, the 0.05 % low concentration of FA was applied to ACD mice induced by 2,4-dinitro-1-fluorobenzene. FA significantly exacerbated inflammatory responses and NLRP3 inflammasome activation, which was confirmed in RAW264.7 macrophages treated with FA at 50 and 100 mu M in vitro. Induction of mitochondrial reactive oxygen species, the common activation signal for NLRP3 inflammasome, was also observed in FA-treated macrophages. Inhibition of NLRP3 by MCC950 significantly attenuated the NLRP3 inflammasome activation induced by 100 mu M FA in vitro and alleviated FA-enhanced inflammatory responses in ACD mice. These results not only demonstrated that FA was able to aggravate the inflammatory responses of ACD by facilitating NLRP3 inflammasome activation in macrophages, which was likely to play important roles in FA-related sensitization, but also indicated that NLRP3 could be targeted to relieve FA-induced inflammation.