ObjectiveTo investigate the synergistic effect of cold stress plus particulate matter 2.5 (PM2.5) co-exposure on the occurrence of respiratory inflammation and the possible post-transcriptional regulation mechanism of cold inducible RNA-binding protein (CIRP).MethodsIn vivo and in vitro experiments were carried out, and the lung tissue specimens from human surgical resection were observed. The rat model and cultured airway epithelial cells 16HBE were respectively divided into four groups (n=8), namely blank control group, 5 °C/18 °C group, PM2.5 group and 5 °C/18 °C+PM2.5 group. The expression of mRNA and protein of representative inflammatory cytokines and CIRP of cultured airway epithelial cells and rat bronchial/pulmonary tissues were respectively detected by ELISA, qPCR, and Western blot. Furthermore, the temporal dynamics of CIRP distribution were observed by cellular immunofluorescence. Finally, immunohistochemical method was used to observe the localization and expression of CIRP in rat and human bronchial/pulmonary tissues at the same time.ResultsIn vivo experiments, the mRNA and protein expression levels of CIRP, interleukin-6, and tumor necrosis factor-α in 5 °C group and PM2.5 group were significantly higher than those in the control group (all P<0.05), while the expression level of mRNA and protein in 5 °C+PM2.5 group were increased most obviously (all P<0.01). The same rule also appeared in the experimental results of each group in the vitro experiment. In addition, CIRP was mainly located in the cell nucleus; compared with the control group, the intracellular shift of CIRP appeared in 18 °C group and PM2.5 group, while the migration phenomenon was most obvious in the 18 °C+PM2.5 group. In the immunohistochemistry of rat bronchus/pulmonary tissue, the expressions of CIRP in the 5 °C group and in the PM2.5 group were significantly higher than those in the control group, and the CIRP expression in 5 °C+PM2.5 group was increased most evidently. Moreover, CIRP was expressed in the bronchial epithelial mucosa of normal people and patients with chronic obstructive respiratory disease (COPD), and it is mainly located in the nucleus of airway mucosal epithelial cells. The CIRP expression of COPD patients was significantly higher than that in the normal population.ConclusionCold stress has a sensitizing effect on airway epithelial inflammatory response induced by PM2.5, and post-transcriptional regulation of CIRP translocation from nucleus to cytoplasm may be an important mechanism.