Zhu Jiang, Zhou Tanfang, Chen Guangfeng, Wu Yuhui, Chen Xia, Song Ya, Tuohetali Ayinula, Gao Huijing, Pang Dongming, Wen Hao, Aimulajiang Kalibixiati
Department of Abdominal Surgery, The Third People Hospital of Xinjiang Uygur Autonomous Region, Urumqi, China.
State Key Laboratory of Pathogenesis, Prevention and Treatment of High Incidence Diseases in Central Asia, Clinical Medicine Institute, The First Affiliated Hospital of Xinjiang Medical University, Urumqi, China.
Front Immunol. 2024 Dec 19;15:1512180. doi: 10.3389/fimmu.2024.1512180. eCollection 2024.
AE and whether the inhibition of the MyD88 inflammatory pathway can enhance Ghrelin expression to collaboratively modulate AE progression remains unclear.
In this study, we evaluated Ghrelin serum levels and changes in TLR4/MyD88/NF-κB pathway proteins and inflammatory factors in AE patients and mouse models at different stages of infection (-4, -8, and -12 weeks). Additionally, we administered the MyD88 inhibitor TJ-M2010-5 intraperitoneally to infected mice to evaluate alterations in inflammation and Ghrelin levels, as well as disease progression.
A decrease in serum Ghrelin levels in AE patients, whereas both Ghrelin and GHSR, along with TLR4/MyD88/NF-κB pathway proteins and markers of M1/M2 macrophage polarization, exhibited increased expression in the inflammatory cell zones surrounding hepatic lesions. Similar findings were observed in -infected mice. M1-type inflammatory expression predominated throughout the infection's progression, with sustained high levels of Ghrelin counteracting inflammation. The TLR4/ MyD88/NF-κB pathway remained suppressed during the first 8 weeks, becoming activated only at 12 weeks. Inhibition of the MyD88 pathway resulted in reduced inflammation levels and upregulated Ghrelin expression, thereby collaboratively regulating the progression of hepatic infection.
These findings suggest an interactive regulation between the MyD88 inflammatory signaling pathway and Ghrelin, indicating that MyD88 inhibition could enhance Ghrelin expression to modulate the progression of infection.
急性肝衰竭（AE）以及抑制髓样分化因子88（MyD88）炎症通路是否能增强胃饥饿素（Ghrelin）表达以协同调节AE进展仍不清楚。
在本研究中，我们评估了AE患者以及处于感染不同阶段（-4周、-8周和-12周）的小鼠模型中血清Ghrelin水平以及Toll样受体4（TLR4）/MyD88/核因子κB（NF-κB）通路蛋白和炎症因子的变化。此外，我们给感染的小鼠腹腔注射MyD88抑制剂TJ-M2010-5，以评估炎症和Ghrelin水平的变化以及疾病进展情况。
AE患者血清Ghrelin水平降低，而在肝损伤周围的炎症细胞区，Ghrelin和生长激素促分泌素受体（GHSR）以及TLR4/MyD88/NF-κB通路蛋白和M1/M2巨噬细胞极化标志物均呈现表达增加。在感染的小鼠中也观察到了类似的结果。在整个感染过程中，M1型炎症表达占主导，持续高水平的Ghrelin可对抗炎症。TLR4/MyD88/NF-κB通路在前8周一直受到抑制，仅在12周时被激活。抑制MyD88通路可降低炎症水平并上调Ghrelin表达，从而协同调节肝脏感染的进展。
这些发现提示MyD88炎症信号通路与Ghrelin之间存在交互调节，表明抑制MyD88可增强Ghrelin表达以调节感染的进展。
