Department of Molecular Bioscience, College of Biomedical Science, Kangwon National University, Chuncheon 24341, Republic of Korea.
Institute of Life Science, Kangwon National University, Chuncheon 24341, Republic of Korea.
Int J Mol Sci. 2023 Feb 23;24(5):4444. doi: 10.3390/ijms24054444.
(), a Gram-positive anaerobic bacterium, proliferates in hair follicles and pores and causes inflammation in the skin of young people. The rapid growth of triggers macrophages to secrete proinflammatory cytokines. Pyrrolidine dithiocarbamate (PDTC) is a thiol compound that exerts antioxidant and anti-inflammatory effects. Although the anti-inflammatory function of PDTC in several inflammatory disorders has been reported, the effect of PDTC on -induced skin inflammation remains unexplored. In the present study, we examined the effect of PDTC on -induced inflammatory responses and determined the mechanism by using in vitro and in vivo experimental models. We found that PDTC significantly inhibited the expression of -induced proinflammatory mediators, such as interleukin-1β (IL-1β), interleukin-6 (IL-6), tumor necrosis factor-α (TNF-α), cyclooxygenase-2 (COX-2), inducible nitric oxide synthase (iNOS), and NOD-like receptor (NLR) pyrin domain-containing 3 (NLRP3), in mouse-bone-marrow-derived macrophage (BMDM) cells. PDTC suppressed -induced activation of nuclear factor-kappa B (NF-κB), which is the major transcription factor for proinflammatory cytokine expression. In addition, we found that PDTC inhibited caspase-1 activation and IL-1β secretion through suppressing NLRP3 and activated the melanoma 2 (AIM2) inflammasome but not the NLR CARD-containing 4 (NLRC4) inflammasome. Moreover, we found that PDTC improved -induced inflammation by attenuating -induced IL-1β secretion in a mouse acne model. Therefore, our results suggest that PDTC has potential therapeutic value for the amelioration of -induced skin inflammation.
痤疮丙酸杆菌是一种革兰氏阳性厌氧细菌，在毛囊和毛孔中繁殖，导致年轻人的皮肤发炎。 的快速生长触发巨噬细胞分泌促炎细胞因子。吡咯烷二硫代氨基甲酸盐 (PDTC) 是一种具有抗氧化和抗炎作用的硫醇化合物。尽管 PDTC 在几种炎症性疾病中的抗炎功能已有报道，但 PDTC 对 诱导的皮肤炎症的影响仍未得到探索。在本研究中，我们使用体外和体内实验模型研究了 PDTC 对 诱导的炎症反应的影响，并确定了其机制。我们发现 PDTC 可显著抑制 -诱导的促炎介质（如白细胞介素-1β (IL-1β)、白细胞介素-6 (IL-6)、肿瘤坏死因子-α (TNF-α)、环氧化酶-2 (COX-2)、诱导型一氧化氮合酶 (iNOS) 和 NOD 样受体 (NLR) 富含吡啶基结构域 3 (NLRP3)）的表达在小鼠骨髓源性巨噬细胞 (BMDM) 细胞中。PDTC 抑制了核因子-κB (NF-κB) 的激活，NF-κB 是促炎细胞因子表达的主要转录因子。此外，我们发现 PDTC 通过抑制 NLRP3 和激活黑素瘤 2 (AIM2) 炎症小体而非 NLR CARD 结构域 4 (NLRC4) 炎症小体来抑制 caspase-1 激活和 IL-1β 分泌。此外，我们发现 PDTC 通过减轻 诱导的 IL-1β 分泌来改善 诱导的炎症在小鼠痤疮模型中。因此，我们的结果表明 PDTC 具有改善 诱导的皮肤炎症的潜在治疗价值。
