Purpose

This study was performed to investigate the effects of interleukin (IL)-4 on adipogenesis and the underlying molecular mechanisms in human meibomian gland epithelial cells (HMGECs).

Methods

HMGECs and human white preadipocytes (HWPs) were cultured and differentiated with or without IL-4. Oil-red O staining, Adipored assay, and LipidTox immunostaining were performed to examine the extent of lipid droplet formation. The expression of signal transducer and activator of transcription 6 (STAT6), phospho-STAT6, peroxisome proliferator activator receptor (PPAR)γ, and sterol regulatory element-binding protein (SREBP)-1 was measured through immunoblotting. Cells were treated with STAT6 inhibitor, which prevents the phosphorylation of STAT6 by IL-4, to determine whether the effects of IL-4 on lipogenesis were altered.

Results

Treatment with IL-4 significantly facilitated lipid production in differentiated HMGECs. Phosphorylation of STAT6 and expression of key adipogenesis-related molecules PPARγ and SREBP-1 were increased after IL-4 treatment. Inhibition of STAT6 phosphorylation suppressed IL-4-mediated lipid synthesis in HMGECs. In contrast, the lipid synthetic effects of IL-4 were not observed in differentiated HWPs.

Conclusions

IL-4 appears to promote lipid synthesis in meibomian gland epithelial cells through the STAT6/PPARγ signaling pathway. This mechanism can serve as a potential therapeutic target for meibomian gland dysfunction.

中文翻译：

---

白细胞介素4通过激活STAT6 /PPARγ信号通路来刺激黑素细胞的脂肪生成。

目的

进行这项研究以研究白介素（IL）-4对人睑板腺上皮细胞（HMGECs）脂肪形成的影响及其潜在的分子机制。

方法

培养HMGEC和人白色前脂肪细胞（HWP），并在有或没有IL-4的情况下进行分化。进行油红O染色，Adipored分析和LipidTox免疫染色以检查脂质液滴形成的程度。通过免疫印迹检测信号转导和转录激活子6（STAT6），磷酸化STAT6，过氧化物酶体增殖物激活子受体（PPAR）γ和固醇调节元件结合蛋白（SREBP）-1的表达。用STAT6抑制剂处理细胞，该抑制剂阻止IL-4使STAT6磷酸化，以确定IL-4对脂肪生成的作用是否改变。

结果

IL-4的治疗显着促进了分化的HMGEC中脂质的产生。IL-4处理后，STAT6的磷酸化和关键的脂肪形成相关分子PPARγ和SREBP-1的表达增加。STAT6磷酸化的抑制抑制HMGECs中IL-4介导的脂质合成。相反，在分化的HWP中未观察到IL-4的脂质合成作用。

结论

IL-4似乎通过STAT6 /PPARγ信号通路促进了睑板腺上皮细胞的脂质合成。该机制可以作为睑板腺功能障碍的潜在治疗靶标。