PTPRO activates TLR4/NF-κB signaling to intensify lipopolysaccharide-induced pneumonia cell injury

Abstract

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.