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Resistance to radiotherapy is a major limitation for the successful treatment of colorectal cancer (CRC). Recently, accumulating evidence supports a critical role of epigenetic regulation in tumor cell survival upon irradiation. Lysine Demethylase 4B (KDM4B) is a histone demethylase involved in the oncogenesis of multiple human cancers but the underlying mechanisms have not been fully elucidated. Here we show that KDM4B is overexpressed in human colorectal cancer (CRC) tumors and cell lines. In CRC cells, KDM4B silencing induces spontaneous double-strand breaks (DSBs) formation and potently sensitizes tumor cells to irradiation. A putative mechanism involved suppression of Signal Transducer and Activator of Transcription 3 (STAT3) signaling pathway, which is essential for efficient repair of damaged DNA. Overexpression of STAT3 in KMD4B knockdown cells largely attenuates DNA damage triggered by KDM4B silencing and increases cell survival upon irradiation. Moreover, we find evidence that transcription factor CAMP Responsive Element Binding Protein (CREB) is a key regulator of KMD4B expression by directly binding to a conserved region in KMD4B promoter. Together, our findings illustrate the significance of CREB-KDM4B-STAT3 signaling cascade in DNA damage response, and highlight that KDM4B may potentially be a novel oncotarget for CRC radiotherapy.

Background Heterogeneity of clinical presentation of chronic obstructive pulmonary disease (COPD) attributes to different pathological basis. High-resolution computed tomography (HRCT) phenotypes of COPD may reflex the pathological basis of COPD indirectly by evaluating the small airway inflammation and emphysema. How the pulmonary function related with different HRCT phenotypes has not been well known. The aim was to explore the features of pulmonary function parameters in the 3 phenotypes. Methods Sixty-three stable COPD patients were allocated in 3 groups based on HRCT findings: phenotype A (absence of emphysema, with minimal evidence of emphysema with or without bronchial wall thickening [BWT]), phenotype E (emphysema without BWT) and phenotype M (emphysema with BWT). The pulmonary function testing was also analyzed. Results The values of forced expiratory volume in 1 second (FEV 1 )/forced vital capacity (FVC%), FEV 1 % and maximum expiratory flows (MEF) 50 % were the highest in phenotype A ( P P 50 /MEF 25 ratio > 4.0 were more prevalence in phenotype A than in E and M (odds ratio = 2.214; P 0.05). The occurrences of RV/TLC% > 40% were higher in phenotype E than in A and M (odds ratio = 3.906; P 0.05). Receiver operating characteristic analysis showed that the cutoff value of MEF 50 /MEF 25 ratio for identifying phenotype A was 2.5, with sensitivity 66.7% and specificity 92.9%. The cutoff value of RV/TLC% for identifying phenotype E was 57.4%, with sensitivity 75.0% and specificity 79.1%. Conclusions The different features of pulmonary function parameters were found in various HRCT phenotypes; MEF 50 /MEF 25 ratio could imply phenotype A, whereas RV/TLC% may be the indicator of phenotype E.

Objective Postoperative ileus (PI) is a common complication following posterior thoraco-lumbar spinal fusion surgery. It usually slows patient’s recovery and increases postoperative morbidity. However, the risk factors associated with PI in patients undergoing posterior thoraco-lumbar spinal fusion surgery are still unclear. The purpose of this study is to investigate the potential risk factors for PI in those patients. Patients and methods A prospective study was conducted and 426 patients received posterior thoraco-lumbar spinal fusion surgery between March 2017 and February 2018 were included in this study. The associations between different clinical factors and PI were analyzed. A logistic regression analysis was performed to detect independent risk factors for PI. The cut-off value, sensitivity and specificity of these independent factors were calculated by receiver operating characteristic (ROC) curve. Results In this study, 8.2% (35/426) of these patients were identified with PI. The average length of postoperative hospital stay was 12.54 ± 6.06 days in patients with PI compared with 8.91 ± 3.81 days in patients without PI (P = 0.001). These results indicated that surgical duration, PLIF approach, blood loss and length of postoperative diet restriction were potential risk factors for PI in patients with thoraco-lumbar spinal fusion surgery. The cut-off values of surgical duration, blood loss and length of postoperative diet restriction were 4.375 h, 750 ml and 9.5 h, respectively. Combination of surgical duration, PLIF approach, blood loss and length of postoperative diet restriction has the highest predictive value for PI (AUC = 0.910, P Conclusion Based on the study, surgical duration, PLIF approach, blood loss and length of postoperative diet restriction were the independent risk factors for PI in patients with posterior thoraco-lumbar spinal fusion surgery. Combined those factors has the highest risk for developing PI.

Patients with chronic obstructive pulmonary disease (COPD) respond poorly to corticosteroids. Histone deacetylase-2 (HDAC-2) plays a pivotal role in many cases of steroid insensitivity. The main aim of this study was to restore the smoking-induced reduction in corticosteroid sensitivity by increasing HDAC-2 activity using low-dose theophylline. Rats were exposed to cigarette smoke (CS) and treated with budesonide and two doses of theophylline. Besides the pathologic examination and cell counting in the bronchoalveolar lavage fluid (BALF), the expression of HDAC-2 and CXC chemokine ligand-8 (CXCL-8) were measured. Airway inflammation induced by CS was demonstrated by pathologic changes of lung tissue and increased level of CXCL-8. CS exposure also markedly decreased HDAC-2 expression. Moreover, a negative correlation was found between HDAC-2 activity and a lung destruction index. The index was restored to control levels with inhaled corticosteroid treatment in combination with a low, not a high, dose of theophylline. These results indicate that low-dose theophylline might provide protection from smoke damage and improve the anti-inflammatory effects of steroids by increasing HDAC-2 activity.

Objective: To analyse the microsatellite instability (MI) and loss of heterozygosity (LOH) in non-small cell lung cancer (NSCLC). Methods: MI and LOH at chromosome 17 were checked in 35 cases of NSCLC tumor-normal paired tissues using four microsatellite markers TP53 (17pl3.1), THRA1 (17qll.2–12), D17S579 (17ql2–21) and D17S855 (17q21) by PCR based analysis. Mutations of P53 exons 5–8 were also tested using PCR-single strand conformation polymorphism (PCR-SSCP) and PCR-denaturing gradient gel electrophoresis (PCR-DGGE) analysis. Results: 22 of 35 tumors (62.8%) displayed MI or LOH. 14 tumors (40.0%) exhibited MI, 11 tumors (31.4%) exhibited LOH, while 3 tumors (8.6%) exhibited MI and LOH concurrently. 23 tumors (65.7%) exhibited P53 gene mutations. The frequency of MI or LOH was obviously higher in the early-stage (stages I and II, 78.9%) than in the advanced-stage (stage III, 43.8%). However, the frequency of MI or LOH had no difference either between high-grade (75.0%) and low-grade (52.6%) differentiated NSCLC or between the tumors with P53 mutations (59.1%) and those without P53 mutations (69.2%). No relationship was observed between the presence of MI or LOH and the histologic subtype of NSCLC. Conclusion: The results suggest that MI and LOH at chromosome 17 may play a significant role in the development of NSCLC. The high frequency of MI or LOH in the early-stage tumors indicates that these genetic alterations could occur early during NSCLC development. Our data also show that the genetic alterations of microsatellite at chromosome 17 was not associated with P53 gene mutations.

Appropriate antimicrobial therapy of community-acquired pneumonia (CAP) is mainly based on the distribution of etiology and antimicrobial resistance of major pathogens. We performed a prospective observational study of adult with CAP in 36 hospitals in China.Etiological pathogens were isolated in each of the centers, and all of the isolated pathogens were sent to Zhongshan Hospital for antimicrobial susceptibility tests using agar dilution.A total of 593 patients were enrolled in this study, and 242 strains of bacteria were isolated from 225 patients. Streptococcus pneumoniae (79/242, 32.6%) was the most frequently isolated pathogen, followed by Haemophilus influenzae (55/242, 22.7%) and Klebsiella pneumoniae (25/242, 10.3%). Totally 527 patients underwent serological tests for atypical pathogens; Mycoplasma pneumoniae and Chlamydia pneumoniae infections were identified in 205 (38.9%) and 60 (11.4%) patients respectively. Legionella pneumophila infections were identified in 4.0% (13/324) of patients. The non-susceptibility rate of isolated Streptococcus pneumoniae to erythromycin and penicillin was 63.2% and 19.1% respectively. Six patients died from the disease, the 30-day mortality rate was 1.1% (6/533).The top three bacteria responsible for CAP in Chinese adults were Streptococcus pneumonia, Haemophilus influenza and Klebsiella pneumonia. There was also a high prevalence of atypical pathogens and mixed pathogens. The resistance rates of the major isolated pathogens were relatively low except for the high prevalence of macrolide resistance in Streptococcus pneumoniae.

To classify the high-resolution CT (HRCT) phenotypes of COPD, and to investigate the clinical characteristics of various phenotypes and the relationship with airway inflammation.Chest HRCT and pulmonary function tests were performed in 84 COPD patients. The patients were classified into 3 phenotypes according to the visual HRCT findings. Exhaled breath condensate was gathered from 30 patients and the interleukin (IL)-6 level was measured by ELISA.The COPD patients were classified into 3 phenotypes: Phenotype A, absence of emphysema, with or without bronchial wall thickening (n = 34); Phenotype E, emphysema without bronchial wall thickening (n = 23); and Phenotype M, emphysema with bronchial wall thickening (n = 27). The 3 phenotypes of COPD showed different characteristics in several aspects. Patients with phenotype A showed a higher body mass index [(25.1 +/- 4.4) kg/m(2) vs phenotype E (22.5 +/- 4.1) kg/m(2) and phenotype M (21.3 +/- 3.4) kg/m(2), F = 6.732, P0.01]. The prevalence of patients with milder dyspnea was lower in phenotype A compared with others (15/34) vs phenotype E (2/23) and phenotype M (6/27), chi(2) = 9.097, P0.05. The patients who complained of severe expectoration in phenotype E were fewer than those in other groups (0/23) vs phenotype A (2/34) and phenotype M (4/27), chi(2) = 8.702, P0.05. The FEV(1)/FVC and FEV(1)% in phenotype M [(53 +/- 14)% and (51 +/- 25)%] were significantly lower as compared with those in other phenotypes [(67 +/- 11)% and (72 +/- 24)% in phenotype A, and (53 +/- 14)% and (52 +/- 26)% in phenotype E], F = 10.252, F = 6.508, P0.01. The ratio of inspiratory capacity to total lung capacity (IC/TLC) in phenotype A was higher [phenotype A (41 +/- 17)%, phenotype E (33 +/- 13)%, phenotype M (28 +/- 13)%, F = 5.964, P0.01], while the ratio of residual volume to total lung capacity (RV/TLC) was lower [phenotype A (37 +/- 9)%, phenotype E (44 +/- 10)%, phenotype M (45 +/- 8)%, F = 6.954, P0.01]. Patients with different phenotypes showed various levels of IL-6 in exhaled breath condensate [phenotype A (19.9 +/- 6.3) ng/L, phenotype E (16.7 +/- 2.1) ng/L, phenotype M (25.6 +/- 4.4) ng/L, F = 7.749, P0.01].Various morphological phenotypes of COPD based on HRCT showed different clinical characteristics and airway inflammation.

To observe the effect of vitamin E (VitE) combined with dexamethasone (DXM) on inflammation of acute lung injury and expression of myosin light chain kinase.Forty female Balb/c mice were randomly divided into 4 groups, a saline control group (1.5 ml/kg), a LPS group (1 mg/kg), a VitE and DXM group (VitE 50 mg/kg, DXM 1 mg/kg), and a VitE group (50 mg/kg). Lung tissue histopathological changes were observed. Immunohistochemistry assays (SABC) were used to determine the myosin light chain kinase (MLCK) immunoreactive cells in the lung tissues, and the MLCK mRNA and the MLCK protein was assayed by RT-PCR and by Western blot, respectively. Means were compared with analysis of variance and Student-Newman-Keuls were used to compare 2 means.Histological examination showed that extensive lung inflammation were seen in the LPS group, which manifested by accumulation of significant numbers of neutrophils, accompanied by marked pulmonary edema and hemorrhage. The inflammation and hemorrhage in the 2 treatment groups were significantly improved. Immunoreactive cells of MLCK numbers in BALF in the control group, the LPS group, the VitE and DXM group, and the VitE group was (1.1 +/- 0.4), (5.6 +/- 2.1), (4.0 +/- 1.0), (4.2 +/- 1.3) x 10(9)/L respectively. Compared with other groups, the difference of LPS group was significant (F = 14. 53, all P0.05). Immunoreactive cells of MLCK located airway epithelial and endothelia in the LPS group were more than which in the control group, decreased immunoreactive cells of MLCK in two treatment groups. Compared with LPS group, the difference of MLCK mRNA expression (A) of lung tissue in two treatment groups was no significant (F = 2.76, all P0.05). Compared with LPS group, the difference of A values of MLCK protein of lung tissue in two treatment groups was statistical significance (F = 12.06, all P0.01).Vitamin E combined with low dose of DXM could effectively inhibit inflammation and expression of MLCK protein in acute lung injury induced by LPS lung. It is suggested that, inhibition of MLCK activation leads to stabilize vascular barrier function and attenuation of pulmonary edema and inflammation, which also suggests a possible role of MLCK in the pathogenesis of acute lung injury.

To investigate the influence of inhibitor of myosin light-chain kinase (MLCK) on the human pulmonary arterial endothelial cell (HPAEC) challenged with lipopolysaccharide (LPS) and LPS induced of acute lung injury (ALI) in mice.HPAECs were cultured in ECM medium and its passages 4-6 were used. After treatment with inhibitor of MLCK (ML-7) for 60 minutes, the HPAECs were incubated in LPS for another 60 minutes, and then cell viability was measured by the methyl thiazolyl tetrazolium (MTT) assay. Immunofluorescence microscope was used to detect phosphorylated-MLCK (p-MLCK) immunoreactive cells. Twenty female BALB/c mice were randomly divided into two groups. The mice of LPS group were exposed to LPS (1 microg/g) through nasal instillation, and the mice of ML-7 group were pretreated with ML-7 before intranasal instillation of LPS. Wet/dry weight (W/D) ratio of lung, bronchoalveolar lavage fluid (BALF) protein content, myeloperoxidase (MPO) activity and histopathological changes of lung tissue were observed. Immunohistochemistry assays were used to determine the status of MLCK and CD11b immunoreactive cells in lung tissue, and expression of MLCK mRNA in lung tissue was assessed by reverse transcription-polymerase chain reaction (RT-PCR). Expression of MLCK protein in lungs was assayed by Western blotting.Compared with LPS group, increased absorbance (A) value of HPAEC was found in ML-7 group (P0.01). Immunoreactive cells of p-MLCK were more reduced in the ML-7 group (P0.05), and W/D ratio of lung, MPO activity and BALF protein content of lung tissue were decreased in ML-7 group (P0.05 or P0.01). Histological examination showed that an extensive lung inflammation was seen in mice of LPS group, with an accumulation of a large number of neutrophils, marked pulmonary edema and hemorrhage, but the inflammation and parenchymal hemorrhage was significantly alleviated in ML-7 group. Both MLCK immunoreactive cells located in endothelium and CD11b in infiltrated inflammatory cells were decreased in ML-7 group compared with those in LPS group. Compared with LPS group, MLCK mRNA and protein expressions (A) in ML-7 group were significantly decreased (both P0.05).ML-7, an MLCK inhibitor, enhances activity of HPAEC induced by LPS and reduces expression of p-MLCK. It also reduces the LPS-induced infiltration of neutrophils in lung tissues, pulmonary edema and expression of MLCK and CD11b protein and MLCK mRNA in lung tissues, demonstrating that inhibition of activation of MLCK, leading to an abatement of phosphorylation of myosin light chain or MLCK, resulting in stabilization of vascular barrier function. The results suggest that MLCK has a crucial role in the pathogenesis of ALI.

Studying the proven and probable invasive pulmonary aspergillosis (IPA) cases of some hospitals in Shanghai to provide evidence for the improvement of IPA clinical diagnosis and therapy.Forty-nine IPA cases were retrospectively analyzed for demography data, host factors, underlying conditions, chest CT, microorganism and histopathology examination, as well as therapy and clinical outcome.Of 49 subjects including 19 (38.8%) proven and 30 (61.2%) probable IPA, 3 patients (6.1%) had no host factors, 25 patients (51.0%) had IPA associated host factors and underlying conditions, while 21 patients (42.9%) had uncertain fundamental diseases. Chest CT evaluation demonstrated that radiological lesions include nodules in 29 patients, patching in 15, mass in 12, consolidation in 10, cavitation in 34, Halo sign in 19, air bronchogram in 18, crescentic sign in 6, bilateral in 33 and multifocal lesions in 38. The yielding rate of fungus culture in sputum was 26.5% (13/49), and in bronchoalveolar lavage fluid was 66.7% (10/15). Eleven of thirty-six patients (30.6%) had positive results of serum galactomannan antigen tests. Nineteen of twenty-one patients (90.5%) were proven as IPA by lung histologic examinations. Aspergillus fumigatus was the most common pathogen 81.0% (17/21). The responding rate to initial anti-fungus therapy was 50% (21/42).Our study suggests that in IPA patients, bilateral, multifocal and nodular lesion could be the most common radiological characteristic, while Halo and crescentic sign occur occasionally. Invasive technologies are more valuable to IPA diagnosis.

Background Smoking is the major cause of airway inflammation in chronic obstructive pulmonary disease(COPD), and smoking cessation is regarded as one of the important strategies for prevention and treatment of the inflammation. The inflammation of the chronic airway may be present and deteriorated even if the COPD patients stop smoking. Whether and how early smoking cessation affects the progress of inflammation is still obscure.This study was conducted to find the appropriate time for smoking cessation to terminate the airway inflammation in rats with smoke-induced chronic bronchitis. Methods A rat model of COPD was established by passively inhaling smoke mixture.Fifty-four young male Sprague-Dawley rats were randomly divided into 9 groups with different periods of smoke exposure and different time points of cessation.The inflammation markers to be detected included inflammatory cells in the bronchoalveolar lavage fluid(BALF),the myeloperoxidose(MPO)activity,the morphologic changes and the expression of ICAM-1 on the airway epithelium. Results When smoking was terminated at early stage,the inflammatory markers and related indexes were different from those of the typical chronic bronchitis group(group M7)(P0.01).The pathologic score of group SC7(2 weeks of smoking cessation after occurrence of typical chronic bronchitis)was not different from that of group MT,and the level of ICAM-1 was still up-regulated(compared to group M7,P0.05).Meanwhile,most of inflammatory cells in BALF were neutrophils compared to other groups(P0.01).When smoking was terminated,the MPO activity was significantly lower than that of group M7(P0.01). Conclusions Smoking cessation at early stage can effectively inhibit the inflammatory reaction of COPD.Once chronic bronchitis occurs,little could be improved by smoking cessation. Chin Med J 2007;120(17):1511-1516

Bronchial asthma is a chronic inflammatory disorder. Long-term inflammation leads to varying degrees of structural changes in the airway wall known as airway reconstruction or remodeling. These structural changes are found in the airways of most patients with prolonged disease. After remodeling, the airway walls show the submucous membrane becomes thick with collagen deposition, and the smooth muscle cells show hyperplasia and hypertrophy. Smooth muscle cells are a vital component of the airway wall, and a major effector cell involved in the course of bronchial contraction. Smooth muscle cell hyperplasia and hypertrophy are important pathological changes in airway remodeling. This study investigated the expression of markers of human airway smooth muscle cells (ASMCs) phenotypic change, which were matrix Gla protein (MGP) and major fibrosis proteins, after in vitro treatment with transforming growth factor-beta(1) (TGF-beta(1)).Human ASMCs were subjected to primary culture in vitro. Ten groups of cells were treated with 100 microg/ml of TGF-beta(1), while the cells in the control groups were treated with 10% fetal bovine serum. After being cultured for 7 d, the cells of both groups were harvested. MGP mRNA expression was detected by RT-PCR. Protein levels of collagen I, III and V were determined by Western blot analysis.Treated with TGF-beta(1), airway smooth muscle cells expressed MGP mRNA greater than controls [(62.3 +/- 13.1)% vs (27.4 +/- 11.4)%, P0.01]. Also, airway smooth muscle cells stimulated by TGF-beta(1) produced more collagen I, III and V than the control group (P0.01).TGF-beta(1) induced expression of collagen III and V, which are early markers of the switch from a contractile to a synthetic phenotype in ASMCs. This induction is an indication that ASMCs have the potential to make this switch and that TGF-beta(1) is involved in airway remodeling.

To identify the phenotype and the gene mutation in a kindred with antithrombin (AT) deficiency.Immuno-nephelometry and chromogenic assay were used to detect the plasma level of AT antigen (AT: Ag) and activity (AT: A), respectively. All the seven exons and intron-exon boundaries of AT gene from the propositus were amplified by PCR and direct sequencing of the PCR pro-ducts was performed. Corresponding PCR fragments from the kindred were also sequenced directly. Megaprimer method was used to construct the mutant AT cDNA expressing vector from normal plasmid pCRII AT cDNA. The normal and mutant AT plasmid were transiently transfected into Cos-7 cells and AT: Ag was detected in supernatant and lysate of transfected cell with ELISA.The plasma level of AT: Ag and AT: A for the propositus were 179 mg/L and 42.3%, respectively. A heterozygous G13328A missense mutation in exon 6 was identified, which led to the substitution of Thr (ACC) 404 for Ala (GCC). The sequencing results from the pedigree suggested that three other members also had the mutation. The level of AT:Ag in supernatant and lysate from cells transfected with mutant AT cDNA was 40% and 68% of that of normal AT cDNA transfected cells.This is an unreported AT gene mutation in China, which causes type I hereditary antithrombin deficiency and thrombosis in the proposita.

To evaluate the efficacy and safety of oseltamivir in the treatment of suspected influenza patients.A randomized, open, control and multiple center trial was conducted among 1176 individuals with suspected influenza. They were randomized either to oseltamivir group (oseltamivir 75 mg, twice daily for 5 days) or control group who were given symptom relief medicine.No difference was found between two groups in influenza symptoms of the patients (P0.05) before the treatment. (1) Oseltamivir treatment significantly reduced the duration of fever about 25 hours post treatment. (2) The AUC score of other symptoms was decreased by 160.21 (about 30.21%), and the duration was shorten by 20 hours. (3) The ratio and duration of antibiotic use in oseltamivir group were less than that of control group (P0.0001 and P0.05). (4) The incident rate of second generation influenza in oseltamivir group was also less than that of control group (P0.0001). (5) Secondary complications such as bronchitis, sinusitis and pneumonia occurred 3.23% in Oseltamivir group and 4.16% in the control group (chi(2) = 1.209, P = 0.272). (6) Digestive symptom such as light nausea were occur in patients who took oseltamivir, there was no difference of side effects rate between two groups (5.18% and 4.16%, chi(2) = 0.680, P = 0.410). (7) 75.68% (28) were confirmed with positive result of virus test in 37 suspected influenza patients.Our data suggests that Oseltamivir is effective and well tolerated in suspected influenza patients. It can reduces the duration and severity of influenza symptom and fever, decrease the incidence of suspected influenza in the contacted population, antibiotic using, and with light side-effect.

There are many candidate genes for chronic obstructive pulmonary disease (COPD). Matrix metalloproteinase-9 (MMP-9) plays an essential role in tissue remodeling and repair associated with development of COPD. In this study we investigated the correlation between MMP-9 gene polymorphism and COPD susceptibility in the Han population of South China.We examined the frequency of polymorphic genotypes of the MMP-9 promoter (-1562C/T) in 100 COPD patients and 98 healthy smokers by restriction fragment length polymorphism.The frequencies of polymorphic genotypes in promoters of MMP-9 were C/C 86%, C/T 14% in COPD group; and C/C 98%, C/T 2% in the control group. There were significant differences between the two groups (P0.01). The allele frequencies were also significantly different between the COPD group and the control group (C allele frequency: 93% vs 99%, T allele frequency: 7% vs 1%, P0.05 respectively).The genetic polymorphism in promoters of MMP-9 gene is associated with the susceptibility to COPD in the Han population of South China.

To study the relation between Interleukin-4 (IL-4), IL-5, IL-13, transforming growth factor-beta(2) (TGF-beta(2)) and airway remodeling and to investigate the effects of Montelukast (MK) on airway inflammation and airway remodeling of asthma.Twenty female BALB/c mice were randomly divided into a remodeling group and a treatment group (MK group), with 10 BALB/c mice in each group. The mice were sensitized by ovalbumin (OVA), and only the MK group was treated with MK (15 mg/kg). The number of total cells and eosinophils in bronchoalveolar lavage fluid (BALF) were counted. Light and electronic microscope were used to detect the pathologic histology and morphologic change. In situ hybridization and reverse transcription-polymerase chain reaction (RT-PCR) were used to measure IL-4, L-5, IL-13, and TGF-beta(2) mRNAs in the lung.The numbers of total cells and eosinophils in BALF of the remodeling group were (5.4 +/- 1.1) x 10(5)/ml and 2.32 +/- 0.20, while those of the treatment group were (3.9 +/- 1.6) x 10(5)/ml and 1.64 +/- 0.32, respectively, the difference being significant (P0.01). Histological and electronic microscopic examination showed extensive airway inflammation, notably accumulation of significant numbers of eosinophils and lymphocytes in the remodeling group. Other features including prominent proliferation of airway epithelial cells protruded like fingers, increased thickness of smooth muscle, hyperplasia of connective tissue, goblet cell hyperplasia and a marked increase in airway mucus secretion with mucus plugging and extensive collagen deposition around the airways were also noted in the remodeling group. In the treatment group, the inflammation was significantly decreased, with decreased production of mucus, decreased collagen and granule of mucus around airway, less proliferation of airway epithelium, smooth muscle hypertrophy and airway spasm. In situ hybridization showed that the expression of IL-13 mRNA and TGF-beta(2) mRNA in the lung of the remodeling group were 24 +/- 7 and 17 +/- 5 respectively, while those of the treatment group were 17 +/- 4 and 10 +/- 3. RT-PCR results showed that the absorbance of IL-4 mRNA and IL-5 mRNA in the lung of the remodeling group were 0.91 and 0.96, while those of the treatment group were 0.22 and 0.35; the differences between the groups were all significant (all P0.01).MK could effectively inhibit airway remodeling, which suggests a possible role of cysteinyl leukotrienes in the pathogenesis of chronic allergic inflammation with fibrosis.