Department of Urology, RenJi Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai, China.
Department of Infectious Diseases, HuaShan Hospital, Fudan University, Shanghai, China.
Front Immunol. 2022 Nov 3;13:1057746. doi: 10.3389/fimmu.2022.1057746. eCollection 2022.
Inflammatory macrophages play a pivotal role in the progression of inflammatory cystitis. Formation of NOD-, LRR- and PYD domains-containing protein 3 (NLRP3) inflammasome triggers the activation of caspase-1/IL-1β signaling cascades to mediate inflammatory response. However, it is not known whether NLRP3 activation in macrophages during cystitis may differ in normal or diabetic setting as well as the importance of it. In this study, we found that NLRP3 levels significantly increased in bladder macrophages in diabetic mice that underwent cystitis. Moreover, bladder macrophages from diabetic mice appeared to have increased their potential of growth, migration and phagocytosis. Furthermore, specific depletion of NLRP3 in macrophages alleviated the severity of cystitis in diabetic mice, but not in non-diabetic mice. Together, our data suggest that NLRP3 depletion in macrophages may be a promising strategy for treating diabetic cystitis.
炎症性巨噬细胞在炎症性膀胱炎的进展中起着关键作用。NOD、LRR 和 PYD 结构域包含蛋白 3(NLRP3)炎性小体的形成触发了半胱天冬酶-1/IL-1β信号级联反应,从而介导炎症反应。然而,目前尚不清楚在膀胱炎期间,巨噬细胞中 NLRP3 的激活是否在正常或糖尿病环境中有所不同,以及其重要性如何。在这项研究中,我们发现,在发生膀胱炎的糖尿病小鼠的膀胱巨噬细胞中,NLRP3 水平显著增加。此外,来自糖尿病小鼠的膀胱巨噬细胞似乎增加了它们的生长、迁移和吞噬能力。此外,巨噬细胞中 NLRP3 的特异性耗竭可减轻糖尿病小鼠膀胱炎的严重程度,但对非糖尿病小鼠无效。总之,我们的数据表明,巨噬细胞中 NLRP3 的耗竭可能是治疗糖尿病性膀胱炎的一种有前途的策略。