OBJECTIVES: To investigate the effect of interferon-λ1 (IFN-λ1) on glucocorticoid (GC) resistance in human bronchial epithelial cells (HBECs) stimulated by respiratory syncytial virus (RSV). METHODS: HBECs were divided into five groups: control, dexamethasone, IFN-λ1, RSV, and RSV+IFN-λ1. CCK-8 assay was used to measure the effect of different concentrations of IFN-λ1 on the viability of HBECs, and the sensitivity of HBECs to dexamethasone was measured in each group. Quantitative real-time PCR was used to measure the mRNA expression levels of p38 mitogen-activated protein kinase (p38 MAPK), glucocorticoid receptor (GR), and MAPK phosphatase-1 (MKP-1). Western blot was used to measure the protein expression level of GR in cell nucleus and cytoplasm, and the nuclear/cytoplasmic ratio of GR was calculated. RESULTS: At 24 and 72 hours, the proliferation activity of HBECs increased with the increase in IFN-λ1 concentration in a dose- and time-dependent manner (P˂0.05). Compared with the RSV group, the RSV+IFN-λ1 group had significant reductions in the half-maximal inhibitory concentration of dexamethasone and the mRNA expression level of p38 MAPK (P<0.05), as well as significant increases in the mRNA expression levels of GR and MKP-1, the level of GR in cell nucleus and cytoplasm, and the nuclear/cytoplasmic GR ratio (P<0.05). CONCLUSIONS IFN-λ1 can inhibit the p38 MAPK pathway by upregulating MKP-1, promote the nuclear translocation of GR, and thus ameliorate GC resistance in HBECs.
Humans ; p38 Mitogen-Activated Protein Kinases/genetics* ; Glucocorticoids/pharmacology* ; Receptors, Glucocorticoid/analysis* ; Dual Specificity Phosphatase 1/physiology* ; Dexamethasone/pharmacology* ; Drug Resistance/drug effects* ; Respiratory Syncytial Viruses ; Interferons/pharmacology* ; MAP Kinase Signaling System/drug effects* ; Epithelial Cells/drug effects* ; Signal Transduction/drug effects* ; Cells, Cultured

OBJECTIVE: To identify the underlying mechanism by which quercetin (Que) alleviates sepsis-related acute respiratory distress syndrome (ARDS). METHODS: In vivo, C57BL/6 mice were assigned to sham, cecal ligation and puncture (CLP), and CLP+Que (50 mg/kg) groups (n=15 per group) by using a random number table. The sepsisrelated ARDS mouse model was established using the CLP method. In vitro, the murine alveolar macrophages (MH-S) cells were classified into control, lipopolysaccharide (LPS), LPS+Que (10 μmol/L), and LPS+Que+acetylcysteine (NAC, 5 mmol/L) groups. The effect of Que on oxidative stress, inflammation, and apoptosis in mice lungs and MH-S cells was determined, and the mechanism with reactive oxygen species (ROS)/p38 mitogen-activated protein kinase (MAPK) pathway was also explored both in vivo and in vitro. RESULTS: Que alleviated lung injury in mice, as reflected by a reversal of pulmonary histopathologic changes as well as a reduction in lung wet/dry weight ratio and neutrophil infiltration (P<0.05 or P<0.01). Additionally, Que improved the survival rate and relieved gas exchange impairment in mice (P<0.01). Que treatment also remarkedly reduced malondialdehyde formation, superoxide dismutase and catalase depletion, and cell apoptosis both in vivo and in vitro (P<0.05 or P<0.01). Moreover, Que treatment diminished the release of inflammatory factors interleukin (IL)-1β, tumor necrosis factor-α, and IL-6 both in vivo and in vitro (P<0.05 or P<0.01). Mechanistic investigation clarifified that Que administration led to a decline in the phosphorylation of p38 MAPK in addition to the suppression of ROS expression (P<0.01). Furthermore, in LPS-induced MH-S cells, ROS inhibitor NAC further inhibited ROS/p38 MAPK pathway, as well as oxidative stress, inflammation, and cell apoptosis on the basis of Que treatment (P<0.05 or P<0.01). CONCLUSION Que was found to exert anti-oxidative, anti-inflammatory, and anti-apoptotic effects by suppressing the ROS/p38 MAPK pathway, thereby conferring protection for mice against sepsis-related ARDS.
Animals ; Sepsis/drug therapy* ; Quercetin/therapeutic use* ; Respiratory Distress Syndrome/enzymology* ; p38 Mitogen-Activated Protein Kinases/metabolism* ; Mice, Inbred C57BL ; Reactive Oxygen Species/metabolism* ; Apoptosis/drug effects* ; Male ; Oxidative Stress/drug effects* ; MAP Kinase Signaling System/drug effects* ; Lung/drug effects* ; Mice ; Lipopolysaccharides ; Macrophages, Alveolar/pathology* ; Inflammation/pathology* ; Protective Agents/therapeutic use*

The aim of this study was to investigate the inhibitory effect and the underlying mechanism of ethacrynic acid (EA) on the contraction in mice. BL-420S force measuring system was used to measure the tension of mouse tracheal rings. The whole cell patch clamp technique was utilized to record the channel currents of airway smooth muscle (ASM) cells. The calcium imaging system was used to determine the intracellular Ca concentration ([Ca]) in ASM cells. The results showed that EA significantly inhibited the high K (80 mmol/L) and acetylcholine (ACh, 100 µmol/L)-induced contraction of mouse tracheal rings in a dose-dependent manner. The maximal relaxation percentages were (97.02 ± 1.56)% and (85.21 ± 0.03)%, and the median effective concentrations were (40.28 ± 2.20) μmol/L and (56.22 ± 7.62) μmol/L, respectively. EA decreased the K and ACh-induced elevation of [Ca] from 0.40 ± 0.04 to 0.16 ± 0.01 and from 0.50 ± 0.01 to 0.39 ± 0.01, respectively. In addition, EA inhibited L-type voltage-dependent calcium channel (LVDCC) and store-operated calcium channel (SOCC) currents in ASM cells, and Ca influx. Moreover, EA decreased the resistance of the respiratory system (Rrs) in vivo in mice. These results indicated that EA inhibits LVDCC and SOCC, which results in termination of Ca influx and decreases of [Ca], leading to relaxation of ASM. Taken together, EA might be a potential bronchodilator.
Animals ; Calcium ; metabolism ; Calcium Channels, L-Type ; Enzyme Inhibitors ; pharmacology ; Ethacrynic Acid ; pharmacology ; Mice ; Muscle Contraction ; drug effects ; Muscle, Smooth ; drug effects ; Respiratory System ; cytology ; drug effects

PURPOSE: During emergence from anesthesia for a craniotomy, maintenance of hemodynamic stability and prompt evaluation of neurological status is mandatory. The aim of this prospective, randomized, double-blind study was to compare the effects of dexmedetomidine and remifentanil on airway reflex and hemodynamic change in patients undergoing craniotomy. MATERIALS AND METHODS: Seventy-four patients undergoing clipping of unruptured cerebral aneurysm were recruited. In the dexmedetomidine group, patients were administered dexmedetomidine (0.5 µg/kg) for 5 minutes, while the patients of the remifentanil group were administered remifentanil with an effect site concentration of 1.5 ng/mL until endotracheal extubation. The incidence and severity of cough and hemodynamic variables were measured during the recovery period. Hemodynamic variables, respiration rate, and sedation scale were measured after extubation and in the post-anesthetic care unit (PACU). RESULTS: The incidence of grade 2 and 3 cough at the point of extubation was 62.5% in the dexmedetomidine group and 53.1% in the remifentanil group (p=0.39). Mean arterial pressure (p=0.01) at admission to the PACU and heart rate (p=0.04 and 0.01, respectively) at admission and at 10 minutes in the PACU were significantly lower in the dexmedetomidine group. Respiration rate was significantly lower in the remifentanil group at 2 minutes (p<0.01) and 5 minutes (p<0.01) after extubation. CONCLUSION: We concluded that a single bolus of dexmedetomidine (0.5 µg/kg) and remifentanil infusion have equal effectiveness in attenuating coughing and hemodynamic changes in patients undergoing cerebral aneurysm clipping; however, dexmedetomidine leads to better preservation of respiration.
Adult ; Aged ; Airway Extubation ; *Anesthesia Recovery Period ; Cough/drug therapy ; *Craniotomy/adverse effects ; Dexmedetomidine/*pharmacology/therapeutic use ; Double-Blind Method ; Female ; Hemodynamics/*drug effects ; Humans ; Male ; Middle Aged ; Piperidines/*pharmacology/therapeutic use ; Prospective Studies ; Reflex/*drug effects ; Respiratory System/blood supply/*drug effects/physiopathology ; Young Adult

Drug-induced hypersensitivity pneumonitis results from interactions between pharmacologic agents and the human immune system. We describe a 54-year-old man with hypersensitivity pneumonitis caused by cephalosporins with identical R1 side chains. The patient, who complained of cough with sputum, was prescribed ceftriaxone and clarithromycin at a local clinic. The following day, he complained of dyspnea, and chest X-ray revealed worsening of inflammation. Upon admission to our hospital, antibiotics were changed to cefepime with levofloxacin, but his pneumonia appeared to progress. Changing antibiotics to meropenem with ciprofloxacin improved his symptoms and radiologic findings. Antibiotics were de-escalated to ceftazidime with levofloxacin, and his condition improved. During later treatment, he was mistakenly prescribed cefotaxime, which led to nausea, vomiting, dyspnea and fever, and indications of pneumonitis on chest X-ray. We performed bronchoalveolar lavage, and the findings included lymphocytosis (23%), eosinophilia (17%), and a low cluster of differentiation (CD) 4 to CD8 ratio (0.1), informing a diagnosis of drug-induced pneumonitis. After a medication change, his symptoms improved and he was discharged. One year later, he was hospitalized for acute respiratory distress syndrome following treatment with ceftriaxone and aminoglycosides for an upper respiratory tract infection. After steroid therapy, he recovered completely. In this patient, hypersensitivity reaction in the lungs was caused by ceftriaxone, cefotaxime, and cefepime, but not by ceftazidime, indicating that the patient's hypersensitivity pneumonitis was to the common R1 side chain of the cephalosporins.
Alveolitis, Extrinsic Allergic* ; Aminoglycosides ; Anti-Bacterial Agents ; Bronchoalveolar Lavage ; Cefotaxime ; Ceftazidime ; Ceftriaxone ; Cephalosporins* ; Ciprofloxacin ; Clarithromycin ; Cough ; Diagnosis ; Drug-Related Side Effects and Adverse Reactions ; Dyspnea ; Eosinophilia ; Fever ; Humans ; Hypersensitivity ; Immune System ; Inflammation ; Levofloxacin ; Lung ; Lymphocytosis ; Middle Aged ; Nausea ; Pneumonia ; Respiratory Distress Syndrome, Adult ; Respiratory Tract Infections ; Sputum ; Thorax ; Vomiting

OBJECTIVETo investigate the effect of anti-miR-145 on human airway smooth muscle cell (HASMC) proliferation and osteopontin systhesis in vitro and explore the mechanisms.

METHODSHASMCs were treated with 10-100 nmol/L anti-miR-145, and the cell proliferation and apoptosis were investigated using a CCK-8 assay and flow cytometry, respectively. The changes in osteopontin synthesis after the treatment was quantified with Western blotting.

RESULTSTreatment with 10 and 50 nmol/L anti-miR-145 significantly promoted the proliferation and osteopontin synthesis in HASMCs (P<0.05 or <0.01), and 50 nmol/L anti-miR-145 obviously inhibited the cell apoptosis (P<0.01).

CONCLUSIONAnti-miR-145 promotes HASMC proliferation and osteopontin synthesis and inhibits HASMC apoptosis in vitro, indicating the important role of anti-miR-145 in the pathogenesis of airway remodeling.

Airway Remodeling ; Apoptosis ; Cell Proliferation ; Cells, Cultured ; Humans ; MicroRNAs ; antagonists & inhibitors ; Myocytes, Smooth Muscle ; drug effects ; Osteopontin ; biosynthesis ; Respiratory System ; cytology

To review long-term respiratory effects of mustard gas on Iranian veterans having undergone Iraq-Iran war. Electronic databases of Scopus, Medline, ISI, IranMedex, and Irandoc sites were searched. We accepted articles published in scientific journals as a quality criterion.The main pathogenic factors are free radical mediators. Prevalence of pulmonary involvement is approximately 42.5%. The most common complaints are cough and dyspnea. Major respiratory complications are chronic obstructive pulmonary disease, bronchiectasis, and asthma. Spirometry results can reveal restrictive and obstructive pulmonary disease. Plain chest X-ray does not help in about 50% of lung diseases. High-resolution CT of the lung is the best modality for diagnostic assessment of parenchymal lung and bronchi. There is no definite curative treatment for mustard lung. The effective treatment regimens consist of oxygen administration, use of vaporized moist air, respiratory physiotherapy, administration of mucolytic agents, bronchodilators, corticosteroids, and long-acting beta-2 agonists, antioxidants, surfactant, magnesium ions, therapeutic bronchoscopy, laser therapy, placement of respiratory stents, early tracheostomy in laryngospasm, and ultimately lung transplantation. High-resolution CT of the lung is the most accurate modality for the evaluation of the lung parenchyma and bronchi. The treatment efficacy of patients exposed to mustard gas depends on patient conditions (acute or chronic, upper or lower respiratory tract involvement). There are various treatment protocols, but unfortunately none of them is definitely curable.
Adult ; Chemical Warfare ; Chemical Warfare Agents ; pharmacology ; Humans ; Iran ; Lung ; diagnostic imaging ; Lung Injury ; chemically induced ; epidemiology ; Male ; Middle Aged ; Mustard Gas ; pharmacology ; Respiratory System ; drug effects ; Survivors ; Tomography, X-Ray Computed ; Veterans ; statistics & numerical data

PURPOSE: If cholesterol in the cell membrane is depleted by treating cells with methyl-beta-cyclodextrin (MbetaCD), the activities of transmembrane receptors are altered in a cell-specific and/or receptor-specific manner. The proinflammatory cytokines, IL-1beta is potent inducers of MUC5AC mRNA and protein synthesis in human airway epithelial cells. Cells activated by IL-1beta showed increased phosphorylation of extracellular signal regulated kinase (ERK) and p38 mitogen-activated protein kinase (MAPK). Thus, we investigated the effects of cholesterol depletion on the expression of MUC5AC in human airway epithelial cells and whether these alterations to MUC5AC expression were related to MAPK activity. MATERIALS AND METHODS: After NCI-H292 cells were pretreated with 1% MbetaCD before adding IL-1beta for 24 hours, MUC5AC mRNA expression was determined by reverse transcription-polymerase chain reaction (RT-PCR) and real time-PCR. Cholesterol depletion by MbetaCD was measured by modified microenzymatic fluorescence assay and filipin staining. The phosphorylation of IL-1 receptor, ERK and p38 MAPK, was analyzed by western blot. RESULTS: Cholesterol in the cell membrane was significantly depleted by treatment with MbetaCD on cells. IL-1beta-induced MUC5AC mRNA expression was decreased by MbetaCD and this decrease occurred IL-1-receptor-specifically. Moreover, we have shown that MbetaCD suppressed the activation of ERK1/2 and p38 MAPK in cells activated with IL-1beta. This result suggests that MbetaCD-mediated suppression of IL-1beta-induced MUC5AC mRNA operated via the ERK- and p38 MAPK-dependent pathway. CONCLUSION: Cholesterol depletion in NCI-H292 cell membrane may be considered an anti-hypersecretory method since it effectively inhibits mucus secretion of respiratory epithelial cells.
Cell Membrane/drug effects/*metabolism ; Cholesterol/*metabolism ; Epithelial Cells/metabolism ; Gene Expression ; Humans ; Mucin 5AC/genetics/*metabolism ; Respiratory System/*metabolism/pathology ; beta-Cyclodextrins/pharmacology

OBJECTIVETo observe the clinical efficacy and the change of airway responsiveness to Chinese medicine (CM) in treating cough variant asthma (CVA).

METHODSNinety-four patients who had confirmed the diagnosis of CVA were selected and randomly assigned to the treatment group and the control group by the blocked randomization method. The ratio of the two groups was 2:1. The treatment group had 63 patients that were treated by CM, lost in 10 cases, 53 patients had finished the trial. The control group had 31 patients that were treated by montelukast tablets and theophylline, lost in 5 cases, 26 patients had finished the trial, two weeks as one therapeutic course. The syndrome efficacy, cough efficacy, symptom score and the airway responsiveness between two groups were observed.

RESULTSThe comparison of the syndrome efficacy: the total effective rate of the treatment group was 90.57% and the control group was 76.92%, and the two groups were significantly different (P<0.05). The comparison of the cough efficacy: the total effective rate of the treatment group was 98.11% and the control group was 80.77%, and the two groups were also significantly different (P<0.05). Syndrome scoring and cough scoring were all significantly lowered, but the airway responsiveness was not significantly lowered.

CONCLUSIONSThe treatment of CM could ease the cough, improve the syndrome, and shows obvious advantages compared with the control group, which is worthy of extensive clinical application.

Adult ; Cough ; drug therapy ; Drugs, Chinese Herbal ; adverse effects ; therapeutic use ; Female ; Humans ; Male ; Respiratory System ; pathology ; Syndrome ; Treatment Outcome

OBJECTIVETo investigate the antiinflammatory activities of aqueous extract of Occimum gratissmium (OGE) with emphasis on expression of proinflammatory cytokines in Lipopolysaccharide (LPS)-stimulated epithelial cell BEAS-2B.

METHODSEffects of OGE on cell viability were determined by MTT assay. mRNA expression were analyzed by and reverse transcription polymerase chain reaction (RT-PCR) and quantitative real-time PCR. Activation of kinase cascades was investigated by immunoblot. Intracellular reactive oxygen species (ROS) was analyzed by flow cytometry.

RESULTSOGE (<200 μg/mL) treatment or pretreatment and following LPS exposure slightly affected viability of BEAS-2B cells. Increase of interleukin (IL)-6 and IL-8 and the elevated level of intracellular ROS in LPS-stimulated BEAS-2B cells were diminished by OGE pretreatment in a dose-dependent manner. OGE suppressed inflammatory response-associated mitogen-activated protein kinases (MAPKs) and Akt activation. Additionally, OGE pretreatment increased level of cellular inhibitor of κBα (IκBα) and inhibited nuclear translocation of nuclear factor kappa B (NF-κB).

CONCLUSIONThese findings indicate that significant suppression of IL-6 and IL-8 expressions in LPS-stimulated BEAS-2B cells by OGE may be attributed to inhibiting activation of MAPKs and Akt and consequently suppressing nuclear translocation of NF-κB.

Cell Nucleus ; drug effects ; metabolism ; Cell Survival ; drug effects ; Cytosol ; drug effects ; metabolism ; Epithelial Cells ; drug effects ; enzymology ; metabolism ; Gene Expression Regulation ; drug effects ; Humans ; I-kappa B Proteins ; metabolism ; Interleukin-6 ; genetics ; metabolism ; Interleukin-8 ; genetics ; metabolism ; Intracellular Space ; drug effects ; metabolism ; Lipopolysaccharides ; pharmacology ; Mitogen-Activated Protein Kinases ; metabolism ; NF-KappaB Inhibitor alpha ; NF-kappa B ; metabolism ; Ocimum ; chemistry ; Phosphorylation ; drug effects ; Plant Extracts ; pharmacology ; Protein Transport ; drug effects ; Proto-Oncogene Proteins c-akt ; metabolism ; RNA, Messenger ; genetics ; metabolism ; Reactive Oxygen Species ; metabolism ; Respiratory System ; cytology ; Water