Division of Pulmonary, Critical Care and Sleep, College of Medicine-Jacksonville, University of Florida, 655 West 11th Street, Jacksonville, FL, 32209, USA.
Department of Cell Biology, University of Miami, Miami, FL, USA.
Lung. 2022 Aug;200(4):463-472. doi: 10.1007/s00408-022-00546-x. Epub 2022 Jun 18.
Alpha-melanocyte stimulating hormone (α-MSH) is known to have anti-inflammatory effects. However, the anti-inflammatory properties of α-MSH on normal bronchial epithelial cells are largely unknown, especially in the context of in vitro sarcoidosis models.
We evaluated the anti-inflammatory effects of α-MSH on two different in vitro sarcoidosis models (lung-on-membrane model; LOMM and three-dimensional biochip pulmonary sarcoidosis model; 3D-BSGM) generated from NBECs and an in vivo sarcoidosis mouse model.
Treatment with α-MSH decreased inflammatory cytokine levels and downregulated type I interferon pathway genes and related proteins in LOMM and 3D-BSGM models. Treatment with α-MSH also significantly decreased macrophages and cytotoxic T-cells counts in a sarcoidosis mice model.
Our results confirm the direct role of type I IFNs in the pathogenesis of sarcoid lung granulomas and highlight α-MSH as a potential novel therapeutic agent for treating pulmonary sarcoidosis.
α-促黑素细胞激素（α-MSH）具有抗炎作用。然而，α-MSH 对正常支气管上皮细胞的抗炎特性在很大程度上尚不清楚，特别是在体外结节病模型的背景下。
我们评估了 α-MSH 对两种不同的体外结节病模型（肺膜模型；LOMM 和三维生物芯片肺结节病模型；3D-BSGM）以及体内结节病小鼠模型中由 NBEC 产生的抗炎作用。
α-MSH 处理降低了 LOMM 和 3D-BSGM 模型中的炎症细胞因子水平，并下调了 I 型干扰素途径基因及其相关蛋白。α-MSH 处理还显著减少了结节病小鼠模型中的巨噬细胞和细胞毒性 T 细胞计数。
我们的结果证实了 I 型 IFNs 在结节病肺肉芽肿发病机制中的直接作用，并强调了 α-MSH 作为治疗肺结节病的潜在新型治疗剂。
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