The Synergistic Effects Of Cold Stress Plus PM2.5 Co-exposure On The Occurrence Of Respiratory Inflammation And The Post-transcriptional Mechanism Of CIRP

Objective:To investigate the synergistic effects of cold stress plus PM2.5 co-exposure on the occurrence of respiratory inflammation and the underlying post-transcriptional mechanism of CIRP.In order to provide a possible intervention target for respiratory inflammation caused by PM2.5 pollution in cold areas.Methods:Combined with observation of human lung tissue specimens were surgically removed,the experiment was respectively divided into 4 groups(n=8)in vitro and in vivo.Cell experiment: namely blank control group(Only the culture medium without fetal bovine serum and without double antibody was used as a negative control),18℃group(the culture medium without fetal bovine serum and without double antibody,18℃),PM2.5 group(the culture medium without fetal bovine serum and without double antibody,PM2.5 suspension),18℃+PM2.5 group(the culture medium without fetal bovine serum and without double antibody,PM2.5 suspension,18℃).Animal experiment :namely blank control group(Inhalation of saline as negative control),18℃group(saline,18℃),PM2.5 group(saline,PM2.5 suspension),18℃+PM2.5 group(saline,PM2.5 suspension,18℃).The expression of mRNA and protein of inflammatory cytokines and CIRP and intracellular shift were detected by ELISA,qPCR,Immunohistochemistry,Western blot and immunofluorescence respectively in vitro and in vivo.Results:In vivo experiments,CIRP,IL-6,TNF-α mRNA and protein expression level in 18°C group and PM2.5 group were significantly higher than that in the control group(all p<0.05),while the expression level of mRNA and protein in 18°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 is 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 expression of CIRP in the 18°C group and in the PM2.5 group were significantly higher than that in the control group,and the CIRP expression in 18°C+PM2.5 group was increased most evidently.Moreover,CIRP was expressed in the bronchial epithelial mucosa of normal people and COPD patients,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.Conclusions:1.CIRP is expressed in the population and is more prominently expressed in patients with chronic airway inflammation,suggesting that CIRP is closely related to the progression and prognosis of a series of inflammatory reactions such as tissue infection and mucus secretion.2.In the low temperature environment,the airway inflammatory response is more agile and the post-transcriptional translation speed is more efficient exposure to PM2.5,suggesting that CIRP mediates the synergistic effects of cold stress plus PM2.5 co-exposure on the occurrence of respiratory inflammation.3.The synergistic effect of acute respiratory damage induced by PM2.5mediated by CIRP translocation-from the nucleus to cytoplasm is an important post-transcriptional cell protection mechanism in eucaryon spontaneously respond to severe environmental stress,which can provide a possible intervention target for respiratory inflammation caused by PM2.5 pollution in cold areas.