■唾液腺功能障碍,通常由唾液腺阻塞引起的炎症引起,是一种普遍的情况。皮质类固醇,以其抗炎和免疫调节特性而闻名,通常在诊所开处方。本研究使用导管结扎小鼠和唾液腺类器官模型研究了地塞米松对阻塞性唾液腺炎恢复的治疗意义和潜在副作用。
■在维持小鼠下颌下管结扎2周后,对导管施用地塞米松后评估功能和病理变化。此外,建立脂多糖和肿瘤坏死因子诱导的涎腺类器官炎症模型,以研究地塞米松的作用和潜在机制。
■地塞米松可促进SG功能恢复,通过增加唾液腺重量和唾液体积,同时减少唾液滞后时间。组织学评估显示,地塞米松治疗减少腺泡细胞萎缩和纤维化。此外,地塞米松抑制促炎细胞因子IL-1β和TNF的表达。在炎症物质诱导的唾液腺类器官炎症模型中,地塞米松恢复腺泡标记,如AQP5基因表达水平,同时抑制促炎细胞因子TNF和IL6,以及趋化因子CCL2,CXCL5和CXCL12的诱导。在来自唾液腺类器官培养物的炎性物质处理的培养基中培养的巨噬细胞表现出促炎极化。然而,地塞米松治疗通过减少M1标志物将它们转向抗炎表型(Tnf,Il6,Il1b,和Cd86)和提升M2标记(Ym1,Il10,Cd163和Klf4)。然而,在体内和体外模型中,高剂量或长时间的地塞米松治疗可诱导腺泡导管上皮化生,并有副作用.
■我们的研究结果表明,皮质类固醇通过调节促炎细胞因子治疗梗阻性唾液腺炎引起的唾液腺功能障碍的有效性。
UNASSIGNED: Salivary gland dysfunction, often resulting from salivary gland obstruction-induced inflammation, is a prevalent condition. Corticosteroid, known for its anti-inflammatory and immunomodulatory properties, is commonly prescribed in clinics. This study investigates the therapeutic implications and potential side effects of dexamethasone on obstructive sialadenitis recovery using duct ligation mice and salivary gland organoid models.
UNASSIGNED: Functional and pathological changes were assessed after administering dexamethasone to the duct following deligation 2 weeks after maintaining ligation of the mouse submandibular duct. Additionally, lipopolysaccharide- and tumor necrosis factor-induced salivary gland organoid inflammation models were established to investigate the effects and underlying mechanisms of action of dexamethasone.
UNASSIGNED: Dexamethasone administration facilitated SG function restoration, by increasing salivary gland weight and saliva volume while reducing saliva lag time. Histological evaluation revealed, reduced acinar cell atrophy and fibrosis with dexamethasone treatment. Additionally, dexamethasone suppressed pro-inflammatory cytokines IL-1β and TNF expression. In a model of inflammation in salivary gland organoids induced by inflammatory substances, dexamethasone restored acinar markers such as AQP5 gene expression levels, while inhibiting pro-inflammatory cytokines TNF and IL6, as well as chemokines CCL2, CXCL5, and CXCL12 induction. Macrophages cultured in inflammatory substance-treated media from salivary gland organoid cultures exhibited pro-inflammatory polarization. However, treatment with dexamethasone shifted them towards an anti-inflammatory phenotype by reducing M1 markers (Tnf, Il6, Il1b, and Cd86) and elevating M2 markers (Ym1, Il10, Cd163, and Klf4). However, high-dose or prolonged dexamethasone treatment induced acino-ductal metaplasia and had side effects in both in vivo and in vitro models.
UNASSIGNED: Our findings suggest the effectiveness of corticosteroids in treating obstructive sialadenitis-induced salivary gland dysfunction by regulating pro-inflammatory cytokines.