Cold‐Inducible RNA‐Binding Protein Causes Prolonged Immersion‐Induced Hypothermic Acute Lung Injury in a Rat Model Through TREM‐1 and NF‐κB

ABSTRACT Hypothermia can cause acute lung injury (ALI). The pathogenetic mechanism of hypothermic ALI involves various proteins. Cold‐inducible RNA‐binding protein (CIRP) is secreted by macrophages or damaged cells and enhances the inflammatory response, resulting in tissue and organ damage. However, it is unclear whether CIRP participates in the development of hypothermic ALI; moreover, the expression pattern of CIRP and its mechanism of action in hypothermic ALI remain unelucidated. To address this issue, we established a stable, long‐term seawater immersion‐induced hypothermic ALI rat model. CIRP expression in the rat lung tissue was downregulated by adeno‐associated virus (AAV) to determine the correlation between the expression of CIRP as well as its related signaling pathway proteins Nuclear factor‐κB (NF‐κB) and Triggering Receptor Expressed on Myeloid Cells‐1 (TREM‐1)and lung injury in a low‐temperature ALI model. A long‐term, seawater immersion‐induced hypothermic ALI rat model was established by immersing the rats in seawater at 18°C for 24 h. As the seawater immersion time increased, the intensity of ALI worsened. CIRP levels in the lung tissue and serum of rats with hypothermic ALI significantly increased in a time‐dependent manner; the levels gradually increased within 24 h and were positively correlated with the expression of inflammatory factors. CIRP knockdown in the rat lung tissue by using AAV significantly decreased the lung coefficient and injury score, reduced the levels of inflammatory factors, and attenuated the expression levels of TREM‐1 and NF‐κB. This finding suggests that CIRP exacerbates the inflammatory response in hypothermic ALI through TREM‐1 and NF‐κB‐related signaling pathways. The present study revealed that CIRP expression increased in the lung tissue and serum of rats with hypothermic ALI in a time‐dependent manner and showed a positive correlation with inflammatory factor release. Knockdown of CIRP expression in the rat lung tissue might reduce inflammation and alleviate lung injury by inhibiting TREM‐1 and NF‐κB signaling pathway proteins.