Background: Previous studies found Propionibacterium acnes (P. acnes) has a strong association with acne inflammation and cell pyroptosis. Because of the various side effects of current acne medicines, it is important to explore alternative drugs with anti-inflammatory activity against P. acnes. we explored the effect of Lutein on P. acnes-induced cell pyroptosis and accelerated the recovery of acne inflammation in vitro and vivo.Methods: Lutein was utilized to expose HaCaT keratinocytes, then we reassessed the effect of Lutein on the cell apoptosis, pyroptotic-associated inflammatory factors and catabolic enzymes in heat-killed P. acnes-treated HaCaT cells. Next, living P. acnes was intradermally injected into the right ears of ICR mice to induce mice with acne inflammation, and the effect of Lutein on living P. acnes-induced inflammation was investigated. Moreover, we explored the mechanism of Lutein on TLR4/NLRP3/Caspase-1 pathways by ELISA, immunofluorescence microscopy, and western blot assay.Results: Heat-killed P. acnes triggered remarkable cell pyroptosis, pyroptotic inflammatory factors and catabolic enzymes in HaCaT cells, including up-regulating interleukin (IL)-1 beta, IL-18, TNF-alpha, MMP3, MMP13, ADAMTS4, and ADAMTS5, TLR4, NLRP3, caspase-1, and the ratio of gasdermin D to cleaved gasdermin D, whereas these effects were suppressed by Lutein. In addition, Lutein effectively improved ear redness, swelling, and the expression of TLR4, IL-1 beta and TNF-alpha in vivo. Finally, NLRP3 activator (nigericin) increased caspase-1, IL-1 beta and IL-18 level, while TLR4 inhibitor (TAK-242) significantly blocked this effect in heat-killed P. acnes-treated cells.Conclusions: Lutein attenuated P. acnes-caused pyroptosis of HaCaTs and the subsequent acne inflammation via the TLR4/NLRP3/Caspase-1 pathway.
基金：
Luzhou Science and Technology Department Project [2020-JYJ-44]; Sichuan Science and Technology Program [2022YFS0631]; National Natural Science Fund of China(NSFC) [82103756]
第一作者机构：[1]Southwest Med Univ, Affiliated Hosp, Dept Dermatol, Luzhou 646000, Peoples R China
共同第一作者：
通讯作者：
推荐引用方式(GB/T 7714)：
Chen Yan,Yi Sha,Wang Qing,et al.Lutein attenuates Propionibacterium acnes-induced inflammation by inhibiting pyroptosis of human keratinocyte cells via TLR4/NLRP3/ Caspase-1 pathway[J].INTERNATIONAL IMMUNOPHARMACOLOGY.2023,117:doi:10.1016/j.intimp.2023.109937.
APA：
Chen, Yan,Yi, Sha,Wang, Qing,Xiong, Haojun,Yuan, Jingyi...&Zhu, Tingting.(2023).Lutein attenuates Propionibacterium acnes-induced inflammation by inhibiting pyroptosis of human keratinocyte cells via TLR4/NLRP3/ Caspase-1 pathway.INTERNATIONAL IMMUNOPHARMACOLOGY,117,
MLA：
Chen, Yan,et al."Lutein attenuates Propionibacterium acnes-induced inflammation by inhibiting pyroptosis of human keratinocyte cells via TLR4/NLRP3/ Caspase-1 pathway".INTERNATIONAL IMMUNOPHARMACOLOGY 117.(2023)
医学