ABSTRACT
BACKGROUND: Cold-inducible RNA-binding protein (CIRP or hnRNP A18) is a multifunctional stress-responsive protein. Our previous study demonstrated that cold stress increased CIRP expression and migrated from the nucleus to the cytoplasm in airway epithelial cells. However, the mechanism through which CIRP migrates from the nucleus to the cytoplasm upon cold stress remains unknown. METHODS: The expression of CIRP in the bronchial epithelium was examined using immunofluorescence, real-time polymerase chain reaction (RT-PCR), and Western blotting. The expression of inflammatory factors interleukin-1ß (IL-1ß), interleukin-6 (IL-6), interleukin-8 (IL-8), and tumor necrosis factor-α (TNF-α) were detected by ELISA and RT-PCR. Transient receptor potential melastatin 8 (TRPM8) receptor function was characterized by Ca2+ imaging. RESULTS: Cold stress upregulated the expression of CIRP, inflammatory factors and promoted the translocation of CIRP from the nucleus to the cytoplasm in normal human bronchial epithelial (NHBE) cells. Cold stress activated the TRPM8/(Ca2+)/PKCα/glycogen synthase kinase 3ß (GSK3ß) signaling cascade, and that inhibition of this signaling pathway attenuated the migration of CIRP from the nucleus to cytoplasm but did not decrease its overexpression induced by cold stress. Knocked down CIRP expression or blocked CIRP migration between the nucleus and cytoplasm significantly decreased inflammatory factor expression. CONCLUSIONS: These results indicate that cold stress leads to the migration of CIRP from the nucleus to the cytoplasm with alteration of expression, which are involved in the expression of inflammatory factors (IL-1ß, IL-6, IL-8 and TNF-α) induced by cold air, through TRPM8/Ca2+/PKCα/GSK3ß signaling cascade.
ABSTRACT
BACKGROUND: Treatment non-adherence is a challenge to achieve asthma control. However, few prospective studies were done for exploring asthma patient adherence in real world. OBJECTIVES: To evaluate treatment adherence and causes of non-adherence in a large asthma Chinese population. To analyze newly-diagnosed patients' adherence first time. METHODS: About 1582 asthma patients' data were collected from 12 study centers in China from February, 2012 to October, 2012. Disease and treatment information of subjects were collected were at first clinic visit, at 4, 12, and 24 weeks after that, follow-up phone calls were carried out for recording subjects' treatment adherence based on their self-reports. Subjects who reported non-adherence were additionally asked to choose the primary non-adherence cause from a list of nine potential causes. RESULTS: Treatment adherence rate of all subjects markedly decreased from 83.3% at week 4 to 42.0% at week 24 after the first clinic visit. Significantly, at week 24, good treatment adherence rate in newly-diagnosed patients was lower than those patients with asthma history (22.9% vs. 63.9%, P < .001). Newly-diagnosed patients were three times more likely to become non-adherence than those patients with asthma history. Female patients had lower treatment adherence rate than male patients (38.3% vs. 45.6%, P = .006). Subjects in 30-39 year age group had the worst treatment adherence (27.3%). The most commonly chosen cause for non-adherence was "relief of symptoms after short-term controller medication use" (43.8%). CONCLUSIONS: Asthma patients' treatment adherence could be improved by improving patient education, doctor/patient partnership, and level of medical service in Chinese population.
