ABSTRACT
Acute or chronic cold exposure exacerbates chronic inflammatory airway diseases, such as chronic obstructive pulmonary disease (COPD) and asthma. Cold-inducible RNA-binding protein (CIRP) is a cold-shock protein and is induced by various environmental stressors, such as hypothermia and hypoxia. In this study, we showed that CIRP gene and protein levels were significantly increased in patients with COPD and in rats with chronic airway inflammation compared with healthy subjects. Similarly, inflammatory cytokine production and MUC5AC secretion were up-regulated in rats following cigarette smoke inhalation. Cold temperature-induced CIRP overexpression and translocation were shown to be dependent on arginine methylation in vitro. CIRP overexpression promoted stress granule (SG) assembly. In the cytoplasm, the stability of pro-inflammatory cytokine mRNAs was increased through specific interactions between CIRP and mediator mRNA 3'-UTRs; these interactions increased the mRNA translation, resulting in MUC5AC overproduction in response to cold stress. Conversely, CIRP silencing and a methyltransferase inhibitor (adenosine dialdehyde) promoted cytokine mRNA degradation and inhibited the inflammatory response and mucus hypersecretion. These findings indicate that cold temperature can induce an airway inflammatory response and excess mucus production via a CIRP-mediated increase in mRNA stability and protein translation.
Subject(s)
Cold-Shock Response , Gene Expression Regulation , Lung/metabolism , Mucus/metabolism , RNA-Binding Proteins/metabolism , 3' Untranslated Regions/genetics , Aged , Animals , Bronchitis/genetics , Bronchitis/metabolism , Bronchitis/physiopathology , Cold-Shock Response/drug effects , Cytokines/genetics , Female , Gene Expression Regulation/drug effects , Humans , Inflammation/genetics , Inflammation/metabolism , Inflammation/physiopathology , Lung/drug effects , Male , Methylation/drug effects , Middle Aged , Mucin 5AC/biosynthesis , Protein Transport/drug effects , Pulmonary Disease, Chronic Obstructive/genetics , Pulmonary Disease, Chronic Obstructive/metabolism , Pulmonary Disease, Chronic Obstructive/physiopathology , RNA-Binding Proteins/genetics , Rats , Smoke/adverse effects , Nicotiana/chemistry , Transcription, Genetic/drug effects , Up-Regulation/drug effectsABSTRACT
Objective To study the influence of theaflavin on the expressions of TLR4 and release of TNF-αand IL-6 in primari-ly cultured rat airway epithelial cells .Methods Lipopolysacchride(LPS) was adopted to establish the in vitro inflammatory injury model of rat airway epithelial cell ,the TNF-αand IL-6 secreted by the airway epithelial cells and the TLR4 protein level in the air-way epithelial cells were detected with ELISA and the expressions of TLR4 mRNA was detected with RT-PCR .Results LPS sig-nificantly induced the airway epithelial cells to secrete TNF-αand IL-6 ,and enhanced the TLR4 mRNA and TLR4 protein expres-sion(P<0 .01) .Theaflavin could inhibit LPS induced TNF-αand IL-6 secretion and TLR4 gene expression(P<0 .05) ,which was related with the theaflavin concentration (P<0 .05) .Conclusion In rat airway epithelial cell culture ,the anti-inflammatory effect of theaflavin may be decrease the release of inflammatory cytokines via inhibiting TLR 4 gene expression and LPS/TLR4 signal trans-duction pathway .
ABSTRACT
Objective: To investigate the effect of tumor necrosis factor-α converting enzyme (TACE) on mucous hypersecretion in inlf ammatory airway. Methods: Mucous hypersecretion model of human lung adenocarcinoma cells A549 was induced by human neutrophil elastase (HNE), and TNF-α converting enzyme inhibitor-1 (TAPI-1), an inhibitor of TACE, was chosen for the inference study. The expression of MUC5AC and TACE was examined. hT e cells were divided into 5 groups: a negative control group, HNE1 (15 nmol/L) group, HNE2 (25 nmol/L) group, HNE3 (50 nmol/L) group and TAPI-1 group. RT-PCR was used to examine MUC5AC and TACE mRNA expression. The protein expression of TACE and MUC5AC was examined by Western blot and ELISA, respectively. Results: HNE induced the TACE and MUC5AC mRNA and protein expression in a dose-dependent manner. Compared with the control group, the increases were all signiifcantly increased in the three dosages of HNE group (P<0.01). The HNE-induced TACE and MUC5AC mRNA and protein expression were dramatically attenuated in the presence of TAPI-1, an inhibitor of TACE (P<0.01). Conclusion: TACE participated cell signalling pathway of airway mucous hypersecretion, and could down regulation the level of inlfammation airway mucous hypersecretion.
ABSTRACT
OBJECTIVE@#To determine the relation between serum myostatin with body mass index (BMI) and PaO₂/PaCO₂ in men with chronic obstructive pulmonary disease (COPD).@*METHODS@#A cohort of outpatients with stable COPD was evaluated. We evaluated the myostatin, PaO₂/PaCO₂ and BMI, and the patients were stratified by BMI. The plasma level of myostatin and PaO₂/PaCO₂ was measured by high sensitivity ELISA or blood gas analysis.@*RESULTS@#PaCO₂ and myostatin increased significantly compared with those in the control group (P<0.05), but PaO₂ decreased significantly. There was positive correlation between myostatin and PaCO₂ (P<0.05), and negative correlation between myostatin and BMI/FEV1/pred value/PaO₂ (P<0.05).@*CONCLUSION@#Patients with higher myostatin levels had a lower BMI, lower PaO₂ and higher PaCO₂, with poor pathogenetic condition and prognosis. Myostatin may be a potential treatment target in patients with chronic obstructive pulmonary disease.
