Dataset Information

Cold-inducible RNA-binding protein migrates from the nucleus to the cytoplasm under cold stress in normal human bronchial epithelial cells via TRPM8-mediated mechanism.

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-1β (IL-1β), 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 3β (GSK3β) 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-1β, IL-6, IL-8 and TNF-α) induced by cold air, through TRPM8/Ca²⁺/PKCα/GSK3β signaling cascade.

SUBMITTER: Mao LP

PROVIDER: S-EPMC8506723 | biostudies-literature | 2021 Sep

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Cold-inducible RNA-binding protein migrates from the nucleus to the cytoplasm under cold stress in normal human bronchial epithelial cells via TRPM8-mediated mechanism.

Mao Liang-Ping LP Jiao Yan Y Xiang Jian-Hua JH Luo Xin-Wei XW He Qian Q Ran Dan-Hua DH Xu Qing Q Lang Chun-Hui CH Chen Ling-Xiu LX

Annals of translational medicine 20210901 18

<h4>Background</h4>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.<h4>Methods</h4>The expression of CIRP in the bronchial epithelium was examined using immunofluorescence, real ...[more]

PMID: 34734022

Similar Datasets

Project description:PURPOSE:Cold air is a major environmental factor that exacerbates asthma. Transient receptor potential melastatin family member 8 (TRPM8) is a cold-sensing channel expressed in the airway epithelium. However, its role in airway inflammation remains unknown. We investigated the role of TRPM8 in innate immune responses in bronchial epithelial cells and asthmatic subjects. METHODS:The TRPM8 mRNA and protein expression on BEAS2B human bronchial epithelial cells was examined by real-time polymerase chain reaction (PCR), immunofluorescence staining and western blotting. Additionally, interleukin (IL)-4, IL-6, IL-8, IL-13, IL-25 and thymic stromal lymphopoietin (TSLP) levels before and after menthol, dexamethasone and N-(4-tert-butylphenyl)-4-(3-chloropyridin-2-yl) piperazine-1-carboxamide (BCTC) treatments were measured via real-time PCR. TRPM8 protein levels in the supernatants of induced sputum from asthmatic subjects and normal control subjects were measured using enzyme-linked immunosorbent assay, and mRNA levels in sputum cell lysates were measured using real-time PCR. RESULTS:Treatment with up to 2 mM menthol dose-dependently increased TRPM8 mRNA and protein in BEAS2B cells compared to untreated cells (P < 0.001) and concomitantly increased IL-25 and TSLP mRNA (P < 0.05), but not IL-33 mRNA. BCTC (10 μM) significantly abolished menthol-induced up-regulation of TRPM8 mRNA and protein and IL-25 and TSLP mRNA (P < 0.01). TRPM8 protein levels were higher in the supernatants of induced sputum from asthmatic subjects (n = 107) than in those from healthy controls (n = 19) (P < 0.001), and IL-25, TSLP and IL-33 mRNA levels were concomitantly increased (P < 0.001). Additionally, TRPM8 mRNA levels correlated strongly with those of IL-25 and TSLP (P < 0.001), and TRPM8 protein levels were significantly higher in bronchodilator-responsive asthmatic subjects than in nonresponders. CONCLUSIONS:TRPM8 may be involved in the airway epithelial cell innate immune response and a molecular target for the treatment of asthma.

Dataset Information

Cold-inducible RNA-binding protein migrates from the nucleus to the cytoplasm under cold stress in normal human bronchial epithelial cells via TRPM8-mediated mechanism.

Background

Methods

Results

Conclusions

Publications

Cold-inducible RNA-binding protein migrates from the nucleus to the cytoplasm under cold stress in normal human bronchial epithelial cells via TRPM8-mediated mechanism.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets