PTPRO 通过激活 TLR4/NF-κB 信号通路加剧脂多糖诱导的肺炎细胞损伤。
PTPRO activates TLR4/NF-κB signaling to intensify lipopolysaccharide-induced pneumonia cell injury.
机构信息
Department of Pediatric, The First Affiliated Hospital of Chengdu Medical College, Chengdu, China.
Department of Pediatric, Huai'an Second People's Hospital, Huai'an, China;
出版信息
Allergol Immunopathol (Madr). 2022 May 1;50(3):119-124. doi: 10.15586/aei.v50i3.589. eCollection 2022.
BACKGROUND
Protein tyrosine phosphatase receptor type O (PTPRO) belongs to the PTP (protein tyrosine phosphatase) family and is widely expressed in parenchymal cells, such as breast and lung epithelial cells. PTPRO has been shown to enhance inflammatory responses and has been implicated in the pathogenesis of inflammation-associated diseases. The role of PTPRO in pneumonia was investigated.
METHODS
Human embryonic lung fibroblasts (HFL1) were treated with increasing concentrations of lipopolysaccharide at 5, 10, or 20 μg/mL to induce inflammatory and apoptotic injuries. Expression of PTPRO was detected by western blot. Inflammation and apoptosis were assessed by ELISA and flow cytometry assays, respectively.
RESULTS
Lipopolysaccharide induced decreased cell viability, and increased inflammation and apoptosis in HFL1. PTPRO was upregulated in HFL1 post lipopolysaccharide treatment, and silencing of PTPRO enhanced lipopolysaccharide-induced cell viability of HFL1, and suppressed the inflammation and apoptosis. However, overexpression of PTPRO aggravated lipopolysaccharide-induced cytotoxicity in HFL1. Overexpression of PTPRO upregulated protein expression of TLR4 and p-p65 in lipopolysaccharide-induced HFL1, while knockdown of PTPRO reduced the level of p-IκBα to downregulate levels of TLR4 and p-p65.
CONCLUSION
PTPRO contributed to pro-inflammatory and pro-apoptotic effects on lipopolysaccharide-induced HFL1 through activation of TLR4/NF-κB signaling.
背景
蛋白酪氨酸磷酸酯酶受体 O（PTPRO）属于蛋白酪氨酸磷酸酯酶（PTP）家族，广泛表达于实质细胞，如乳腺和肺上皮细胞。已有研究表明，PTPRO 可增强炎症反应，并与炎症相关疾病的发病机制有关。本研究旨在探讨 PTPRO 在肺炎中的作用。
方法
用不同浓度（5、10 或 20μg/ml）的脂多糖处理人胚肺成纤维细胞（HFL1）以诱导炎症和凋亡损伤，用 Western blot 检测 PTPRO 的表达。通过 ELISA 和流式细胞术检测炎症和凋亡。
结果
脂多糖诱导 HFL1 细胞活力降低，炎症和凋亡增加。脂多糖处理后 HFL1 中 PTPRO 上调，沉默 PTPRO 增强了脂多糖诱导的 HFL1 细胞活力，并抑制了炎症和凋亡。然而，过表达 PTPRO 加重了脂多糖诱导的 HFL1 细胞毒性。PTPRO 的过表达上调了脂多糖诱导的 HFL1 中 TLR4 和 p-p65 的蛋白表达，而 PTPRO 的敲低降低了 p-IκBα 的水平，从而下调了 TLR4 和 p-p65 的水平。
结论
PTPRO 通过激活 TLR4/NF-κB 信号通路，对脂多糖诱导的 HFL1 发挥促炎和促凋亡作用。
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