Objective To observe the levels of malonaldehyde (MDA) , interleukin-8 (IL-8) and tumor necrosis factor-α(TNF-α) in lung tissues of subjects with or without chronic obstructive pulmonary disease (COPD) , and investigate their roles in the the pathogenesis of COPD. Methods The content of MDA, IL-8 and TNF-αin lung tissues of smokers with COPD (n=9) , ex-smokers with COPD (n=8) , non-smokers with COPD (n=7) , healthy smokers (n=9) , healthy ex-smokers (n=8) and healthy nonsmokers (n=6) was measured with enzyme-linked immunosorbent assay ( ELISA) and corrected by creatinine. Results The levels of MDA, IL-8 and TNF-α in lung tissues of the COPD patients were significantly higher than those in the healthy subjects (Plt;0.05) , which were also significantly higher in the smokers when compared with the non-smokers (Plt;0.05) , whether suffering from COPD or not. In the COPD patients, not the levels of IL-8 but MDA and TNF-αin lung tissues of the smokers were significantly higher than those in the ex-smokers (Plt;0.05) ; whereas in the healthy cases, no statistical significance was revealed between the smokers and the ex-smokers on the levels of MDA and IL-8 in lung tissues except TNF-α( Pgt;0.05) . Conclusion The abnormal increase of MDA, IL-8 and TNF-αin lung tissues caused by chronic smoking may play an important role in the the pathogenesis of COPD.
Objective To investigate the effects of tobacco smoke exposure on histone deacetylase 2 (HDAC2),interleukin-8(IL-8)and tumor necrosis factor-α(TNF-α)expression in peripheral blood of patients with lung adenocarcinoma and analyze the relationships among them. Methods Seventy-three cases diagnosed as lung adenocarcinoma were collected in the First Affiliated Hospital and Affiliated Tumor Hospital of Guangxi Medical University from April 2014 to March 2015.All patients underwent lung function test preoperatively.Fourteen healthy volunteers without tobacco smoke exposure and chronic obstructive pulmonary disease (COPD)were recruited as healthy control.According to the lung function and tobacco smoke exposure,all cases were divided into four groups,ie. a healthy control group (group A,14 cases),a group without tobacco smoke exposure and COPD(group B,19 cases),a group with tobacco smoke exposure and without COPD(group C,33 cases),and a group with tobacco smoke exposure and COPD(group D,21 cases).The expressions of HDAC2 mRNA,IL-8 mRNA and TNF-α mRNA in peripheral blood mononuclear cells (PBMCs)were detected by real-time polymerase chain reaction (PCR).The contents of IL-8 and TNF-α in serum were detected by ELISA. Results Compared with group A,the HDAC2 mRNA expression in PBMCs had no difference in group B(P>0.05),and was down-regulated significantly in group C and D (P<0.05),which in group D was the most obvious.Compared with group A,the expressions of IL-8 mRNA and TNF-α mRNA in PBMCs and the contents of IL-8 and TNF-α in serum were significantly higher in all lung adenocarcinoma patients(all P<0.05),and the up-regulation was more obvious in group D.The relative expression of HDAC2 mRNA in PBMCs showed no significant difference with respect to age,gender or TNM stage (P>0.05).IL-8 and TNF-α in PBMCs and serum showed no significant difference with respect to age and gender (P>0.05),and were higher in the patients with TNM stage Ⅲ lung adenocarcinoma than those with stage Ⅰ and Ⅱ(P<0.05),with no obvious difference between stage Ⅰ and stage Ⅱ (P>0.05). Conclusion Tobacco smoke exposure causes lower expression of HDAC2 and over-expression of IL-8 and TNF-α in peripheral blood of patients with lung adenocarcinoma,can aggravate inflammatory response especially when complicated with COPD,which may be related to the prognosis of lung adenocarcinoma.
ObjectiveTo investigate the expression and significance of cysteine-rich protein 61 (Cyr61) in patients with chronic obstructive pulmonary disease (COPD).MethodsBetween September 2017 and September 2018, 27 patients with benign tumor needing to surgical therapy, were divided into COPD group (15 patients) and non-COPD group (12 patients), according to lung function. Lung tissues were selected at the distance at least 5 cm from the tumor. The levels of Cyr61, interleukin-8 (IL-8) and monocyte chemoattractant protein-1 (MCP-1) in serum were determined by enzyme-linked immunosorbent assay. Meanwhile, the expressions of Cyr61 in lung tissues were measured by immunohistochemistry technology between two groups. Furthermore, correlations among Cyr61, IL-8, MCP-1, smoking index, forced expiratory volume in the 1st second as percentage of predicted values (FEV1%pred), scores of COPD Assessment Test (CAT) were analyzed.ResultsSerum Cyr61, IL-8, MCP-1 levels were significantly higher in patients with COPD than in the non-COPD group (P<0.05), (2409.80±893.87)pg/mL, (76.27±10.53)pg/mL, (173.67±42.64)pg/mL vs. (1065.42±158.83)pg/mL, (57.33±8.29)pg/mL, (138.42±27.62)pg/mL, respectively. By immunohistochemistry technology, the expression levels of Cyr61 in lung epithelial cells and in lung macrophage cells of COPD patients were higher than in the non-COPD group (P<0.01). Positive correlations were found between serum IL-8, serum MCP-1, CAT scores, smoking index and serum Cyr61 (r=0.674, 0.566, 0.602, and 0.755, P=0.006, 0.028, 0.018, and 0.003, respectively) in COPD group. Furthermore, in COPD group, there were also positive correlations between serum IL-8, serum MCP-1, CAT scores, smoking index and intrapulmonary Cyr61 (r=0.542, 0.635, 0.809, and 0.580, P=0.037, 0.011, 0.001, and 0.038 respectively). Inverse correlation was found between serum Cyr61 and FEV1%pred (r=–0.772, P<0.01), and the same as between intrapulmonary Cyr61 and FEV1%pred (r=–0.683, P<0.01).ConclusionsCyr61 highly expresses in serum and in lung tissues of patients with COPD, and its expression is correlated with lung function of patients. The results indicate that Cyr61 may interact with IL-8 and MCP-1 in the pathogenesis of chronic obstructive pulmonary disease.
Objective To investigate the role of macrophage stimulating protein (MSP) in the pathogenesis of chronic obstructive pulmonary disease (COPD). Methods Ninety subjects were recruited from health examination center, outpatient or inpatient department in Affiliated Hospital of North Sichuan Medical College from July 2013 to December 2013. They were divided intoahealthy control group, a stable COPD group, and an acute exacerbation of COPD (AECOPD) group with 30 subjects in each group. The levels of MSP, interleukin-6 (IL-6), IL-8 and tumor necrosis factor-α (TNF-α) in the plasma of all subjects, as well as the levels of MSP in the induced sputum of the AECOPD and the stable COPD patients were assessed by enzyme-linked-immuno-sorbent assay. Results The concentrations of MSP, IL-6, IL-8 and TNF-α in the plasma of the patients with COPD were obviously higher than those of the healthy controls (P<0.05) while much higher in AECOPD patients than those in stable COPD patients (P<0.01).The concentration of MSP in the induced sputum of the patients with AECOPD was higher than that in the stable COPD patients (P<0.01). The concentrations of MSP in the serum and induced sputum as well as serum levels of IL-6, IL-8 and TNF-α in the patients with COPD were negatively correlated with the level of FEV1%pred. The concentrations of MSP in the serum and induced sputum in the COPD patients were positively correlated with the concentrations of IL-6, IL-8 and TNF-α. Conclusions The concentrations of serum and induced sputum MSP, and the serum concentrations of IL-6, IL-8 and TNF-α in COPD patients are related to the severity of the disease. MSP may play an important role in the pathogenesis of COPD. The mechanism might be mainly involved in the regulation of airway inflammation.
Objective To analyze the relationship of serum IL-17, IL-8 levels and BODE index in patients with stable COPD, and investigate the clinical value of serum IL-17 and IL-8 in evaluating disease severity and prognosis. Methods A comparative study was performed in40 clinically stable COPD patients and 40 matched healthy individuals. The serum levels of IL-17 and IL-8 in both groups were measured. Correlation analysis was performed between serum IL-17, IL-8 levels and BODE index in the patients with stable COPD. Results The serumlevels of IL-17 and IL-8 in the COPD group were ( 114. 02 ±34. 84) pg/mL and ( 102. 67 ±31. 55) pg/mL, increased significantly compared with those in the healthy group which were ( 73. 22 ±14. 66) pg/mL and ( 35. 36 ±5. 04) pg/mL ( P lt;0. 05) respectively. Both of serum IL-17 and IL-8 levels were positively correlated with BODE index in the patients with stable COPD ( r = 0. 782, r = 0. 924, P lt;0. 001) . Conclusions High levels of serumIL-17 and IL-8 implies active inflammation in patients with stable COPD. Detection of serumIL-17 and IL-8 can help evaluate disease severity and prognosis.
ObjectiveTo observe the effect of interleukin-8 (IL-8) on the adhesion and migration of retinal vascular endothelial cells (RCEC). MethodsA cell experiment. Human RCEC (hRCEC) was divided into normal control group (N group), advanced glycation end product (AGE) treatment group (AGE group), and AGE-induced combined IL-8 antagonist SB225002 treatment group (AGE+SB group). The effect of AGE on IL-8 expression in hRCEC was observed by Western blot. The effect of SB225002 on hRCEC migration was observed by cell scratch assay. The effects of SB225002 on leukocyte adhesion and reactive oxygen species (ROS) on hRCEC were detected by flow cytometry. Student-t test was performed between the two groups. One-way analysis of variance was performed among the three groups. ResultsCompared with group N, the expression level of IL-8 in cells of AGE group was significantly increased, with statistical significance (t=25.661, P＜0.001). Compared with N group and AGE+SB group, cell mobility in AGE group was significantly increased (F=29.776), leukocyte adhesion number was significantly increased (F=38.159, 38.556), ROS expression level was significantly increased (F=22.336), and the differences were statistically significant (P＜0.05). ConclusionIL-8 antagonist SB225002 may down-regulate hRCEC adhesion and migration by inhibiting ROS expression.
Objective To investigate the effects of TiotropiumBromide on airway inflammation in a rat model of chronic obstructive pulmonary disease( COPD) . Methods Thirty Wistar rats were randomly divided into three groups. Group A received normal breeding as normal control. Group B and group C received LPS( 200 μg, intratracheally injected at the 1st and the 14th day) and tobacco exposure( from the 2nd day to the 30th day except the 14th day) to establish COPD model. And group C received a nebulized dose of Tiotropium Bromide( 0. 12 mmol / L, 10 minutes) 30 minutes before the tobacco exposure each time. Airway resistance and compliance were measured before sacrificed. Histological examination was performed with Hematoxylin-Eosin staining. The concentrations of IL-8 and LTB4 , total and differential cells counts in bronchoalveolar lavage fluid( BALF) were examined, and the concentrations of IL-8 and LTB4 in blood serum were also examined by ELISA. Results Severe lung inflammation and decreased lung function were demonstrated in the rats in the group B compared with those in the group A. The inflammatory cell counts in BALF, and the levels of IL-8 and LTB4 in BALF and serum were significantly increased in the group B compared with those in the group A. Tiotropium Bromide administration improved the parameters above. Conclusions The results suggest that Tiotropium Bromide can alleviate the lung inflammation and improve the lung function in a rat COPD model. These effects may be exerted through reducing the mediators of inflammation.
Objective To investigate the effects of dust mite allergen Derp1 on the expressions of IL-6 and IL-8 in primary rat bronchial epithelial cells. Methods The primary rat bronchial epithelial cells were divided into a control group and three experimental groups. In the experimental groups, the cells were cultured with 3 different concentrations of Derp1 ( 1, 5, 10 μg/mL) for 3 different time ( 4, 8, 24 h) .Inverted microscope was employed to observe the morphological changes of bronchial epithelial cells and intercellular space, and supernatants were assayed for IL-6 and IL-8 with ELISA. Results Complete flattening of single cells layer was observed in the control group. In the experimental groups, the cells treated with Derp1 allergen showed no obvious changes in the cell morphology and intercellular space. However,There was a significant change in the level of cytokines production compared with the control group. The levels of IL-6 and IL-8 began to rise at 4 h, and reach to high level at 8 h, especially in the 5 and 10 μg/mL groups ( P lt;0. 01) . In the 24h group, the concentrations further increased but not reach statistical difference compared with 8h group ( P gt; 0. 05) . Conclusions The Derp1 allergen can stimulate the release of inflammatory cytokines such as IL-6 and IL-8 fromthe rat trachea- bronchia epithelial cells. It is suggested that dust mite allergen -induced cytokines may play important roles in the pathogenesis of allergic asthma.
Objective To explore clinical significance of interleukin-8 (IL-8), clarada protein 16 (CC16), and intercellular adhesion molecule-1 (ICAM-1) in exhaled breath condensate (EBC) and serum samples collected from patients with acute respiratory distress syndrome (ARDS). Methods A total of 45 ARDS patients were assigned into a mild ARDS group (n=20), a moderate ARDS group (n=15) and a severe ARDS group (n=10) based on the Berlin definition. During the same study period, 45 healthy subjects were recruited as control. Serum and EBC levels of IL-8, CC16 and ICAM-1 were detected on the first and fifth day of admission. Results Compared with the control group, serum and EBC IL-8, CC16 and ICAM-1 were significantly higher in the ARDS groups (P<0.05). Serum and EBC IL-8 levels increased with the severity of ARDS, whereas no significant difference was detected between the three groups (P>0.05). Compared with the mild group and the moderate group, serum and EBC CC16 levels were significantly higher in the severe ARDS group. At the first day after admission, serum ICAM-1 was higher in the severe and moderate ARDS groups than that in the mild ARDS group (P<0.05). Meanwhile, EBC ICAM-1 was significantly different between the three groups (P<0.05). At the fifth day after admission, different EBC ICAM-1 was identified between the severe ARDS group and the other two groups (P<0.05). Regardless of ARDS severity, there were no significant differences in serum and EBC IL-8 and CC16 levels at the first and fifth days after admission (P>0.05). However, serum and EBC ICAM-1 at the first and fifth days showed significant difference (except in the mild ARDS group) (P<0.05). The levels of ICAM-1 in serum and EBC of death group were significantly higher than those of survival group (P<0.05). Conclusion Serum and EBC IL-8, CC16 and ICAM-1 are of significance in diagnosis and prognosis evaluation of ARDS.
Objective To explore the therapeutic effect of angiotensin-converting enzyme 2( ACE2) on pulmonary edema after sea-water drowning.Methods Twenty-four Wistar rats were randomly divided into 3 groups, ie. a control group, a seawater drowning group, and an ACE2 treatment group. The rats in the seawater drowning group and the ACE2 treatment group were infused sea-water into their lungs. Then the rats in the ACE2 treatment group were intraperitoneally injected with recombinant rat ACE2. All rats were killed at the time point of 3 hours. Rat arterial blood gas was analyzed and wet /dry weight ratio of lung tissue was measured. The IL-8 content in lung tissue was measured with enzyme linked immunosorbent assay. Pathological changes of lung tissue were observed under light microscope. Results Acute lung injury induced by seawater drowning was successfully reproduced in the rats. The PaO2 in the seawater drowning group was significantly lower than that in the control group and the ACE2 treatment group [ ( 52. 34 ±2. 69) mmHg vs. ( 96. 40 ±3. 47) mm Hg and ( 64. 58 ±3. 42) mm Hg, P lt;0. 05] . The lung W/D ratio and IL-8 level in the seawater drowning group were significantly higher than those in the control group and the ACE2 treatment group ( 8. 30 ±0. 24 vs. 4. 49 ±0. 19 and 5. 65 ±0. 25, P lt; 0. 05; 1112. 2 ±40. 02 vs. 440. 39 ± 4. 06 and 858. 56 ±9. 92, P lt;0. 05) . Lung pathological examination revealed hemorrhage and hyaline membrane formation, alveolar and interstitial edema in the seawater drowning group while those changes significantly relieved in the ACE2 treatment group. Conclusion ACE2 treatment has therapeutic effects on acute lung injury induced by seawater drowning.