Mycoplasma pneumoniae regulates the expression of GP130 in lung epithelial cells through apoptosis and TLR4/ NF-κB pathway during infection

• Published in: Microbial pathogenesis 2024-12, Vol.197, p.107072, Article 107072
• Main Authors: Zhang, Zhikun, Shi, Dawei, Dou, Haiwei, Wan, Ruijie, Yuan, Qing, Tu, Peng, Xin, Deli
• Format: Article
• Language: English
• Subjects: adhesion; Apoptosis; blood serum; Cell Line; Cytokine Receptor gp130 - genetics; Cytokine Receptor gp130 - metabolism; Down-Regulation; Epithelial Cells - metabolism; Epithelial Cells - microbiology; epithelium; gene expression; Gene Expression Regulation; GP130; heat; Humans; interleukin-6; Interleukin-6 - genetics; Interleukin-6 - metabolism; Lung - metabolism; Lung - microbiology; Lung - pathology; lungs; Mycoplasma pneumoniae; Mycoplasma pneumoniae - genetics; NF-kappa B - metabolism; NF-κB; pathogenesis; Pneumonia, Mycoplasma - metabolism; Pneumonia, Mycoplasma - microbiology; proteasome inhibitors; protein content; Signal Transduction; TLR4; Toll-Like Receptor 4 - genetics; Toll-Like Receptor 4 - metabolism; trypsin
• ISSN: 0882-4010; 1096-1208; 1096-1208
• DOI: 10.1016/j.micpath.2024.107072

In previous study, lower levels of serum GP130 were reported in children with MPP. GP130 is an important signal transducer, the down regulation of which may influence host immune responses. In this study, we aimed to analyze the regulatory mechanism of GP130 during MP infection. Firstly, the mRNA and protein levels of GP130 both decrease and then increase with increasing multiplicity of infection (MOI: 1 to 40) of MP. The lowest levels of GP130 were detected at MOI of 5. Then, heat treated MP but not trypsin treated MP or MP extracted proteins show regulatory effect to the expression of GP130. These indicate that the down regulation of GP130 is related to protein mediate adhesion process of MP. Gene expression analysis revealed that MP affected apoptosis and the TLR4 pathway in infected cells, and the mRNA level of IL-6 was correlated with that of GP130. Further, Z-VAD-FMK (pan-caspase inhibitor) can suppress the apoptosis induced by MP infection and restore GP130 at protein level. Further studies revealed that MP infection promoted TLR4 internalization but did not activate the NF-κB pathway. The levels of surface TLR4 showed correlation with the transcription of IL-6 and GP130. TAK242 (TLR4 inhibitor) and PS341 (proteasome inhibitor) can restore the decreased transcription of GP130, both of which were able to promote NF-κB pathway activation in MP-infected cells. These suggested that the regulation of TLR4/NF-κB pathway and induced apoptosis post MP infection are involved in the down-regulation of GP130 at transcription and protein levels, respectively. The infection of Mycoplasma pneumoniae promotes the internalization of TLR4, which reduces the transcription of GP130. Meanwhile, apoptosis induced by Mycoplasma pneumoniae infection may degrade GP130 protein through Caspases. [Display omitted] •Mycoplasma pneumoniae (MP) infection promotes internalization of TLR4.•Mycoplasma pneumoniae affects GP130 transcription by TLR4 pathway.•MP infection decreases the protein levels of GP130 at multiplicity of infection of 5–20.