Abstract
Patients with Mycoplasma pneumoniae (MP) infections have markedly higher C-reactive protein (CRP). We investigated how CRP contributes to lung epithelial cell death following MP infection. CRP levels were assessed in children diagnosed with Mycoplasma pneumoniae pneumonia (MPP) and A549 lung epithelial cells infected with MP. A549 cells were genetically modified to overexpress CRP. Effects on cell viability, apoptosis, reactive oxygen species (ROS) and mitochondrial membrane potential (ΔΨm) were evaluated. The expression of proteins implicated in the p38 MAPK/mitochondrial apoptotic pathway was analyzed. The protective effects of the p38 MAPK inhibitor SB203580 and the mitochondrial protector cyclosporin A (CsA) were assessed. CRP levels were elevated in both MPP patients and MP-infected A549 cells compared to controls. Increased apoptosis and reduced cell viability were observed in MP-infected cells. CRP overexpression led to upregulation of proteins in the p38 MAPK/mitochondrial apoptosis pathway, increased cytoplasmic Cyt C, decreased Tom 20 and ΔΨm, and elevated ROS. Pretreatment with SB203580 or posttreatment with CsA reduced apoptosis and mitochondrial damage and enhanced cell survival. Increased CRP levels during MP infection promote lung epithelial cell death by activating the p38 MAPK/mitochondrial apoptosis pathway. Targeting this pathway could offer therapeutic potential to reduce lung damage in MPP patients.IMPORTANCEThis study provides critical information in understanding the pathophysiological mechanisms for MP infections concerning CRP in mediating lung epithelial cell injury. This study outlines the significant increase in MP-infected patients and shows its direct involvement in cell apoptosis through the p38 MAPK/mitochondrial apoptosis pathway. By explaining this pathway, the possibility of targeting CRP and its connected signaling mechanisms to devise therapeutic interventions for the amelioration of lung damage in MP-infected patients is brought to light. The implications of such data are not merely in the added knowledge for disease pathobiology but also it brings new promise for novel intervention strategies to result in improved clinical outcomes. The elucidation of specific molecular targets inside the apoptosis pathway heralds a new area regarding the direction of future research and clinical application for humanity in general and concerning the broader relevance and impact of this study on respiratory diseases.