Department of Respiratory Medicine, Navy General Hospital of the PLA, No. 6 Fucheng Road, Beijing, 100037, China.
Department of Neurology, The First Hospital of Changsha, Changsha, 430100, People's Republic of China.
Inflammation. 2017 Dec;40(6):1983-1999. doi: 10.1007/s10753-017-0639-9.
Previous studies have demonstrated paralemmin-3 (PALM3) participates in Toll-like receptor (TLR) signaling. This study investigated the effect of PALM3 knockdown on lipopolysaccharide (LPS)-induced acute lung injury (ALI) and its underlying mechanisms. We constructed a recombinant adenoviral vector containing short hairpin RNA for PALM3 to knockdown PALM3 expression. A transgene-free adenoviral vector was used as a negative control. The ALI rat model was established by LPS peritoneal injection at 48-h post-transfection. Results showed that downregulation of PALM3 improved the survival rate, attenuated lung pathological changes, alleviated pulmonary edema, lung vascular leakage and neutrophil infiltration, inhibited the production of proinflammatory cytokines and activation of nuclear factor κB and interferon β regulatory factor 3, and promoted the secretion of anti-inflammatory cytokine interleukin-10 and expression of suppressor of cytokine signaling-3 in the ALI rat model. However, PALM3 knockdown had no effect on TLR4, myeloid differentiation factor 88 (MyD88), and Toll-interleukin-1 receptor domain-containing adaptor inducing interferon β (TRIF) expression. Moreover, PALM3 knockdown reduced the interaction of TLR4 with MyD88 or TRIF induced by LPS in rat lungs. Therefore, the downregulation of PALM3 protected rats from LPS-induced ALI and its mechanisms were partially associated with the modulation of inflammatory responses and inhibition of TLR4/MyD88 and TLR4/TRIF complex formation.
先前的研究表明， paralemmin-3（PALM3）参与 Toll 样受体（TLR）信号转导。本研究探讨了 PALM3 敲低对脂多糖（LPS）诱导的急性肺损伤（ALI）的影响及其潜在机制。我们构建了一个包含 PALM3 短发夹 RNA 的重组腺病毒载体，以敲低 PALM3 表达。转基因-free 腺病毒载体被用作阴性对照。转染后 48 小时通过 LPS 腹腔注射建立 ALI 大鼠模型。结果表明，下调 PALM3 可提高存活率，减轻肺组织病理学变化，缓解肺水肿、肺血管渗漏和中性粒细胞浸润，抑制促炎细胞因子的产生和核因子 κB 和干扰素 β 调节因子 3 的激活，并促进抗炎细胞因子白细胞介素-10 的分泌和抑癌信号-3 在 ALI 大鼠模型中的表达。然而，PALM3 敲低对 TLR4、髓样分化因子 88（MyD88）和 Toll-白细胞介素-1 受体域包含衔接诱导干扰素 β（TRIF）的表达没有影响。此外，PALM3 敲低降低了 LPS 诱导的 TLR4 与 MyD88 或 TRIF 在大鼠肺中的相互作用。因此，下调 PALM3 可保护大鼠免受 LPS 诱导的 ALI 的影响，其机制部分与炎症反应的调节以及抑制 TLR4/MyD88 和 TLR4/TRIF 复合物的形成有关。
