Tu Chen, Wang Shuang, Hu Xiao, Wang Wenju, Dong Yingying, Xiao Shengxiang, Wang Xiaopeng
Department of Dermatology, Second Affiliated Hospital of Xi'an Jiaotong University, Xi'an, Shaanxi, 710004, China.
Department of Dermatology, Second Affiliated Hospital of Lanzhou University, Lanzhou, Gansu, 730030, China.
Cell Biol Int. 2016 Dec;40(12):1357-1365. doi: 10.1002/cbin.10693. Epub 2016 Nov 2.
Bacterial infection is an important factor that can trigger and exacerbate psoriasis. The protein triggering receptor expressed on myeloid cells type-1 (TREM-1) is overexpressed in psoriasis and decreased after a successful treatment. Hypoxia inducible factor-1α (HIF-1α), subunit of the transcription factor HIF-1, has participated in angiogenesis and inflammation in psoriasis. Increased expressions of TREM-1 and HIF-1α are associated with the infection of microbial pathogens. However, the association between TREM-1 and HIF-1α still needs to be elucidated. Results of immunofluorescence showed an overexpression of TREM-1 and HIF-1α in HaCaT keratinocytes exposed to 1 µg/mL of lipopolysaccharide (LPS). Particularly, silencing of TREM-1 expression by siRNA suppressed the inducible effect of LPS on phosphoinositide 3-kinase (PI3 K)/Akt, the critical transduction mediator, and HIF-1α. Furthermore, the PI3 K inhibitor wortmannin effectively blocked the increased level of HIF-1α induced by LPS. However, there was no significant change in LPS-induced expression of TREM-1. Expressions of TREM-1, HIF-1α, and phosphorylated Akt proteins were further examined by real-time PCR and Western blot, respectively. Our data suggest that TREM-1 and HIF-1α are expressed on keratinocytes and could be upregulated by bacterial infection. Moreover, LPS-induced TREM-1 has an ability to mediate the expression of HIF-1α in HaCaT cells through the PI3 K/Akt pathway. Our study provides new insights into the possible mechanism of TREM-1 and HIF-1α in psoriasis.
细菌感染是引发和加重银屑病的一个重要因素。髓样细胞触发受体-1（TREM-1）在银屑病中过度表达，成功治疗后其表达水平下降。转录因子低氧诱导因子-1（HIF-1）的亚基HIF-1α参与了银屑病的血管生成和炎症反应。TREM-1和HIF-1α的表达增加与微生物病原体感染有关。然而，TREM-1与HIF-1α之间的关联仍有待阐明。免疫荧光结果显示，在暴露于1μg/mL脂多糖（LPS）的HaCaT角质形成细胞中，TREM-1和HIF-1α过度表达。特别地，通过小干扰RNA（siRNA）沉默TREM-1表达可抑制LPS对关键转导介质磷酸肌醇3激酶（PI3K）/蛋白激酶B（Akt）和HIF-1α的诱导作用。此外，PI3K抑制剂渥曼青霉素可有效阻断LPS诱导的HIF-1α水平升高。然而，LPS诱导的TREM-1表达没有显著变化。分别通过实时荧光定量PCR和蛋白质免疫印迹法进一步检测了TREM-1、HIF-1α和磷酸化Akt蛋白的表达。我们的数据表明，TREM-1和HIF-1α在角质形成细胞上表达，并且可被细菌感染上调。此外，LPS诱导的TREM-1能够通过PI3K/Akt途径介导HaCaT细胞中HIF-1α的表达。我们的研究为TREM-1和HIF-1α在银屑病中的可能机制提供了新的见解。
