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Randomized Controlled Trial
. 2025 Sep;83(3):3225-3238.
doi: 10.1007/s12013-025-01704-7. Epub 2025 Mar 7.

DNA Receptor Toll-Like Receptor 9 Signaling Pathway Plays a Major Immunomodulatory Role in Neonatal Acute Lung Injury by Inhibiting Inflammatory Response and Oxidative Stress

Weiyun Liu  1 , Yunping Zheng  2 , Liyan Liu  3
Affiliations
Randomized Controlled Trial

DNA Receptor Toll-Like Receptor 9 Signaling Pathway Plays a Major Immunomodulatory Role in Neonatal Acute Lung Injury by Inhibiting Inflammatory Response and Oxidative Stress

Weiyun Liu et al. Cell Biochem Biophys. 2025 Sep.

Abstract

To investigate the clinical efficacy of neonatal acute lung injury (NALI) and the mechanistic role of the DNA sensor Toll-like receptor 9 (TLR9) signaling pathway in treatment, Methods: This study enrolled 76 cases of NALI, randomly divided into 38 cases in the experimental group (intravenous injection of human immunoglobulin on the basis of nasal continuous positive airway pressure ventilation treatment) and 38 cases in the control group (nasal continuous positive airway pressure ventilation treatment). The pulmonary function parameters (forced vital capacity (FVC), forced expiratory volume in 1 s (FEV1), and FEV1/FVC), TLR9 signaling pathway-related proteins and mRNA levels (TLR9, MyD88, p38), inflammatory factors (C-reactive protein (CRP), interleukin (IL)-1β, tumor necrosis factor (TNF)-α), and immune function indicators (immunoglobulin (Ig)A, IgG, IgM) were compared between the two groups. Pearson correlation analysis was conducted to examine the relationship between TLR9 signaling pathway protein expression and immune function indicators.After treatment, the pulmonary function parameters FVC, FEV1, and FEV1/FVC in neonates in the experimental group were considerably higher than those in the control group (P < 0.05). The serum levels of inflammatory factors CRP, IL-1β, and TNF-α in the experimental group of neonates following treatment were significantly lower than those in the control group (P < 0.05). After treatment, the levels of immune function indicators IgA, IgG, and IgM in neonates in the experimental group were considerably lower than those in the control group (P < 0.05). The protein expression levels of TLR9 showed a highly significant positive correlation with neonatal immune function indicators IgA, IgG, and IgM levels (P < 0.001). MyD88 protein expression exhibited a significant positive correlation with neonatal immune function indicators IgA, IgG, and IgM levels (P < 0.05). p38 protein expression demonstrated a significant positive correlation with neonatal immune function indicators IgA, IgG, and IgM levels (P < 0.05). In summary, the potential role of DNA receptor TLR9 signaling pathway-related proteins in the treatment of neonates with lung injury has been explored. The changes in the expression levels of TLR9/MyD88/p38 are associated with the production or regulation of immunoglobulins, and this association shows a certain correlation with the clinical efficacy in neonates with lung injury.

Keywords: Acute lung injury; DNA sensor; Immune function; Neonates; Pulmonary function parameters; TLR9 signaling pathway.

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Conflict of interest statement

Compliance with ethical standards. Conflict of interest: The authors declare no competing interests. Ethics approval and consent to participate: The study was approved by the local ethics committee of the Xinyu Peoples Hospital. All experiments were performed in accordance with relevant guidelines and regulations such as the Declaration of Helsinki and the patients signed the informed consent form and agreed to be published.

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