Department of Respiratory and Critical Care Medicine, The Second Hospital of Hebei Medical University, Shijiazhuang, Hebei 050000, P.R. China.
Department of Respiratory and Critical Care Medicine, The Second Hospital of Hebei Medical University, Shijiazhuang, Hebei 050000, P.R. China.
Int J Mol Med. 2023 Apr;51(4). doi: 10.3892/ijmm.2023.5235. Epub 2023 Mar 10.
Irisin is a hormone‑like myokine that regulates cell signaling pathways and exerts anti‑inflammatory effects. However, the specific molecular mechanisms involved in this process are currently unknown. The present study explored the role and mechanisms underlying the functions of irisin in alleviating acute lung injury (ALI). The present study used MH‑S, an established murine alveolar macrophage‑derived cell line, and a mouse model of lipopolysaccharide (LPS)‑induced‑ALI to examine the efficacy of irisin against ALI and , respectively. Fibronectin type III repeat‑containing protein/irisin was expressed in the inflamed lung tissue, but not in normal lung tissue. Exogenous irisin reduced alveolar inflammatory cell infiltration and pro‑inflammatory factor secretion in mice following LPS stimulation. It also inhibited the polarization of M1‑type macrophages and promoted the repolarization of M2‑type macrophages, thus reducing the LPS‑induced production and secretion of interleukin (IL)‑1β, IL‑18 and tumor necrosis factor‑α. In addition, irisin reduced the release of the molecular chaperone heat shock protein 90 (HSP90), inhibited the formation of nucleotide‑binding and oligomerization domain‑like receptor protein 3 (NLRP3) inflammasome complexes, and decreased the expression of caspase‑1 and the cleavage of gasdermin D (GSDMD), leading to reduced pyroptosis and the accompanying inflammation. On the whole, the findings of the present study demonstrate that irisin attenuates ALI by inhibiting the HSP90/NLRP3/caspase‑1/GSDMD signaling pathway, reversing macrophage polarization and reducing the pyroptosis of macrophages. These findings provide a theoretical basis for understanding the role of irisin in the treatment of ALI and acute respiratory distress syndrome.
鸢尾素是一种类似激素的肌因子，可调节细胞信号通路并发挥抗炎作用。然而，目前尚不清楚这一过程中涉及的具体分子机制。本研究探讨了鸢尾素在缓解急性肺损伤（ALI）中的作用和机制。本研究使用 MH-S，一种已建立的鼠肺泡巨噬细胞衍生细胞系，以及脂多糖（LPS）诱导的小鼠 ALI 模型，分别研究了鸢尾素对 ALI 的疗效。纤维连接蛋白 III 型重复蛋白/鸢尾素在炎症肺组织中表达，但在正常肺组织中不表达。外源性鸢尾素可减少 LPS 刺激后小鼠肺泡炎症细胞浸润和促炎因子的分泌。它还抑制 M1 型巨噬细胞的极化，并促进 M2 型巨噬细胞的再极化，从而减少 LPS 诱导的白细胞介素（IL）-1β、IL-18 和肿瘤坏死因子-α的产生和分泌。此外，鸢尾素降低了分子伴侣热休克蛋白 90（HSP90）的释放，抑制核苷酸结合寡聚化结构域样受体蛋白 3（NLRP3）炎性小体复合物的形成，并降低半胱天冬酶-1 的表达和 Gasdermin D（GSDMD）的切割，从而减少细胞焦亡和伴随的炎症。总的来说，本研究的结果表明，鸢尾素通过抑制 HSP90/NLRP3/caspase-1/GSDMD 信号通路，逆转巨噬细胞极化并减少巨噬细胞的细胞焦亡，从而减轻 ALI。这些发现为理解鸢尾素在治疗 ALI 和急性呼吸窘迫综合征中的作用提供了理论依据。
