interleukin-8 and Adenocarcinoma--Bronchiolo-Alveolar

The present study examined the effects of formic acid and acetic acid on human adenocarcinoma-derived alveolar basal epithelial A549 cells. The organic acids were administered either individually or in combination, into either the culture medium (aqueous phase) or the gaseous phase of an air-liquid interface. When either of the acids was administered into the aqueous phase, cell proliferation was inhibited at doses of 1-10 mg/mL. In contrast, when the acids were administered either individually or in combination, into the gaseous phase of the air-liquid interface, cell proliferation was not altered. Under the gaseous phase administration, acetic acid and mixed acids caused a slight increase, decrease and increase on the interleukin-8 production, the mRNA expression of the heme oxygenase-1 (HO-1) gene and the HO-1 production, respectively, at one or more time points. The results therefore indicated that organic acids might be less reactive in the gaseous phase than in the aqueous phase. However, acetic acid in the gaseous phase either individually or in combination with formic acid exerts some effects on A549 cells.

Topics: A549 Cells; Acetic Acid; Adenocarcinoma, Bronchiolo-Alveolar; Cell Proliferation; Dose-Response Relationship, Drug; Formates; Gases; Gene Expression; Heme Oxygenase-1; Humans; Interleukin-8; Lung Neoplasms; RNA, Messenger; Vehicle Emissions

Chronic inflammation is considered as an important factor in the pathogenesis of lung cancer. The presence of inflammatory cells and higher levels of pro-inflammatory cytokines in the tumor microenvironment and their surrounding tissues is gaining much importance in research.. One hundred ninety NSCLC cases and 200 age, smoking and sex matched controls were evaluated for association of IL-8 -251 (rs4073) and IL-8 -845 (rs2227532) in our population. Restriction fragment length polymorphism (RFLP) was used followed by direct sequencing for the detection of SNPs.. The IL-8 -845 polymorphism was not found in our population. No significant association was observed between the IL-8 -251 AT genotypes and IL-8 -25 AA genotypes and NSCLC (p=0.05) in our population. The IL-8 -251 A allele was also non-significant (p=0.05) in NSCLC patients.. In conclusion, this report reveals lack of association between IL-8 - 251 A/T polymorphism and NSCLC in our Kashmir Valley population.

Topics: 3' Untranslated Regions; Adenocarcinoma; Adenocarcinoma, Bronchiolo-Alveolar; Carcinoma, Large Cell; Carcinoma, Non-Small-Cell Lung; Carcinoma, Squamous Cell; Case-Control Studies; Female; Follow-Up Studies; Genotype; Humans; India; Interleukin-8; Lung Neoplasms; Male; Middle Aged; Neoplasm Staging; Polymerase Chain Reaction; Polymorphism, Genetic; Polymorphism, Restriction Fragment Length; Prognosis

In this study an in vitro exposure test to investigate toxicological effects of the volatile disinfection by-product trichloramine and of real indoor pool air was established. For this purpose a set-up to generate a well-defined, clean gas stream of trichloramine was combined with biotests. Human alveolar epithelial lung cells of the cell line A-549 were exposed in a CULTEX(®) device with trichloramine concentrations between 0.1 and 40 mg/m(3) for 1 h. As toxicological endpoints the cell viability and the inflammatory response by the cytokines IL-6 and IL-8 were investigated. A decreasing cell viability could be observed with increasing trichloramine concentration. An increase of IL-8 release could be determined at trichloramine concentrations higher than 10 mg/m(3) and an increase of IL-6 release at concentrations of 20 mg/m(3). Investigations of indoor swimming pool air showed similar inflammatory effects to the lung cells although the air concentrations of trichloramine of 0.17 and 0.19 mg/m(3) were much lower compared with the laboratory experiments with trichloramine as the only contaminant. Therefore it is assumed that a mixture of trichloramine and other disinfection by-products in the air of indoor pool settings contribute to that effect.

Topics: Adenocarcinoma, Bronchiolo-Alveolar; Air Pollutants; Air Pollution, Indoor; Cell Line; Chlorides; Cytokines; Disinfection; Environmental Monitoring; Epithelial Cells; Humans; Interleukin-6; Interleukin-8; Lung; Lung Injury; Nitrogen Compounds; Swimming Pools

The presence of increased numbers of tumor-infiltrating neutrophils is associated with poorer outcome in patients with adenocarcinoma of the bronchioloalveolar (BAC) subtype. We evaluated the role of inflammatory environment on C-X-C chemokine tumor production.. Bronchoalveolar lavage from 31 consecutive patients with adenocarcinoma of the BAC subtype as well as tumor and normal pulmonary tissue samples. A549 BAC cell line. Peripheral blood mononuclear cells (PBMC), polymorphonuclear neutrophils (PMN) and alveolar macrophages (AM).. Elisa measurements and immunohistochemical studies of ENA-78, IL-8, IL-1beta and TNF-alpha. RNA isolation, reverse transcription, and PCR amplification of ENA-78 and IL-8.. C-X-C peptides were expressed by tumor cells of all the tumor specimens tested. ENA-78 and IL-8 were also expressed by AM. To better understand the regulation of the C-X-C production, BAC cell line was cultured alone or with inflammatory cells. PBMC upregulated both tumor ENA-78 and IL-8 mRNA expression and protein release whereas AM only upregulated ENA-78 mRNA expression and protein release; PMN had no effect. Anti-human IL-1beta antibodies (ab) inhibited the A549 ENA-78 and IL-8 production stimulated by PBMC-CM. Anti-human TNF-alpha ab inhibited A549 ENA-78 production stimulated by AM-CM. IL-1beta and TNF-alpha were expressed in vivo by inflammatory cells, although TNF-alpha was also expressed by tumor cells.. This work emphasizes the role of the host inflammatory response in promoting tumor growth in vivo.

Topics: Adenocarcinoma, Bronchiolo-Alveolar; Bronchoalveolar Lavage Fluid; Case-Control Studies; Cell Line, Tumor; Chemokine CXCL5; Chemokines, CXC; Female; Humans; Interleukin-1; Interleukin-8; Lung Neoplasms; Macrophages, Alveolar; Male; Middle Aged; Monocytes; Neutrophils; Tumor Necrosis Factor-alpha

To determine whether tumor necrosis factor (TNF)-alpha-induced interleukin (IL)-8 production by pulmonary alveolar epithelial cells is blocked by perfluorocarbon (PFC).. Controlled, laboratory investigation of IL-8 production by pulmonary alveolar epithelial cells after exposure to PFC in vitro.. University research laboratory.. The human alveolar epithelial cell line with pulmonary type II (A549) cell properties.. The A549 cells on a polycarbonate porous filter were stimulated either on the apical or the basolateral side with TNF-alpha. To determine TNF-alpha-induced IL-8 production, IL-8 was measured by using a human IL-8 kit in both control and experimental groups.. TNF-alpha stimulation induced a large increase in IL-8. When PFC was added to the medium immediately after TNF-alpha stimulation, PFC separated the medium from the cells and IL-8 production was markedly reduced (TNF-alpha alone, 8342+/-470 pg vs. TNF-alpha followed by PFC, 417+/-88 pg, p < .05). Preincubation of A549 cells with PFC for 24 hrs before stimulation with TNF-alpha followed by removal of PFC did not affect IL-8 production (8834+/-204 vs. 8342+/-470 pg; p = NS). When added to the lower chamber, TNF-alpha also induced IL-8 production unaffected by the addition of PFC to the upper chamber. The decrease in TNF-alpha-induced IL-8 production depended on the time of PFC administration after the initiation of TNF-alpha stimulation. The earlier PFC was added, the more pronounced the diminution was in IL-8.. PFC appears to function as a physical barrier, thus reducing cytokines produced by alveolar epithelial cells in vitro. This mechanism may partially explain the decreased inflammatory response observed during liquid ventilation in models of acute lung injury.

Topics: Adenocarcinoma, Bronchiolo-Alveolar; Cell Communication; Drug Interactions; Epithelial Cells; Fluorocarbons; Humans; Interleukin-8; Lung Neoplasms; Pulmonary Alveoli; Time Factors; Tumor Cells, Cultured; Tumor Necrosis Factor-alpha

Tumor infiltrate, predominantly constituted by lymphocytes, may represent an important prognostic factor in bronchioloalveolar carcinoma (BAC), in addition to tumor extension and histological type. In the present study, we determined the presence, the origin, and the prognostic importance of neutrophils that also participate in leukocyte infiltrates of BAC. Neutrophil alveolitis was determined immunohistochemically in both lung biopsies and bronchoalveolar lavage (BAL) fluid samples from 29 patients with histologically proved BAC. The local expression of interleukin (IL)-8 was determined by immunohistochemical and immunoenzymatic techniques. Neutrophil counts were analyzed in relation to the clinical outcome of patients by the Kaplan-Meier method and Cox's univariate and stepwise multivariate models. Lymphocytes and neutrophils dominated the inflammatory cell population in the lower respiratory tract of patients with BAC. Neutrophils were located mainly in the alveolar lumen and seldom in alveolar wall whereas lymphocytes were exclusively present in alveolar wall. A relationship was observed between the number of neutrophils and the level of IL-8 in BAL fluid suggesting the involvement of that chemokine in neutrophil recruitment. The tumor cells were the predominant cells that appeared to express IL-8 by immunolocalization. The presence of increased numbers of neutrophils was significantly associated with a poorer outcome in patients with BAC (P = 0.02). In a multivariate analysis, the neutrophil percentage in BAL fluid was an independent predictor of clinical outcome. The risk of death was increased substantially (rate ratio, 5.2; 95% confidence interval, 1.1 to 24.7) among patients with BAL neutrophil percentage of > or = 39% (median of the distribution) as compared with the others. In BAC, neutrophils accumulate in the alveolar lumen. Elaboration of IL-8 by tumor cells may be responsible for this event, which is associated with a significantly higher risk of death.

Topics: Adenocarcinoma, Bronchiolo-Alveolar; Adult; Aged; Aged, 80 and over; Bronchoalveolar Lavage Fluid; Female; Humans; Interleukin-8; Lung Neoplasms; Male; Middle Aged; Neutrophils; Pneumonia; Prognosis; Pulmonary Alveoli

Epidemiologic data show that air pollution particulates cause adverse pulmonary health effects, especially in individuals with preexisting lung disease. We sought to model in vitro preexisting lung inflammation in order to investigate the hypothesis that "primed" lung epithelial cells will exhibit enhanced phlogistic responses [e.g., interleukin-8 (IL-8) production] to particulate air pollution. Exposure of tumor necrosis factor alpha (TNF-alpha) primed or control A549 cells to the air pollution particulates, residual oil fly ash (ROFA), and the known pathogenic dust alpha-quartz, but not inert TiO2, caused increased IL-8 production in primed cells compared to normal cells in a concentration-dependent manner (particle concentration range 0-200 microg/ml). We hypothesized that oxidant mechanisms may be involved in the cellular response to particulates. Addition of the antioxidant N-acetylcysteine (NAC, 1.0 mM) decreased ROFA and alpha-quartz-mediated IL-8 production by approximately 50% in normal and TNF-alpha-primed A549 cells. In addition, exposure of A549 cells to ROFA caused a substantial (and NAC inhibitable) increase in oxidant levels as measured by fluorometry (DCFH oxidation). These data suggest that (1) lung epithelial cells primed by inflammatory mediators can show enhanced cytokine production after exposure to air pollution particulates, and (2) oxidant stress is a key mechanism for this response.

Topics: Acetylcysteine; Adenocarcinoma, Bronchiolo-Alveolar; Air Pollution; Antioxidants; Carbon; Chromans; Coal Ash; Dose-Response Relationship, Drug; Epithelial Cells; Flow Cytometry; Fluoresceins; Free Radical Scavengers; Humans; Industrial Waste; Interleukin-8; Lung; Lung Neoplasms; Oxidative Stress; Particle Size; Particulate Matter; Petroleum; Piperazines; Pneumonia; Quartz; Titanium; Tumor Cells, Cultured; Tumor Necrosis Factor-alpha

Ozone is one of the most common air pollutants humans routinely inhale. We have previously shown that in vitro ozone exposure induces the DNA-binding activities of NF-kappaB and NF-IL6 as well as the expression of interleukin 8 in respiratory epithelial cells. In this study, we investigated intracellular signaling steps mediating ozone-induced inflammatory mediator release. A549 cells, a type II like alveolar epithelial cell line, were exposed in vitro to air or 0.1 ppm of ozone in the presence of several kinase inhibitors. Exposure to ozone increased interleukin 8 expression and transcription factor activities in a protein tyrosine kinase (PTK)-dependent and protein kinase A (PKA)-dependent, yet protein kinase C (PKC)-independent, manner. Furthermore, ozone-induced PTK and PKA activities but failed to induce PKC activity. In addition, our results suggest that ozone-induced PTK and PKA activities were reactive oxygen intermediate dependent and occurred in parallel, because specific inhibitors for PTK and PKA failed to block the other kinase's activity. These results indicate that PTK and PKA activities are early events in the signal transduction cascade mediating the ozone-induced activation of NF-kappaB and NF-IL6 as well as the release of interleukin 8.

Topics: Adenocarcinoma, Bronchiolo-Alveolar; CCAAT-Enhancer-Binding Proteins; Cyclic AMP-Dependent Protein Kinase Type II; Cyclic AMP-Dependent Protein Kinases; DNA-Binding Proteins; Enzyme Activation; Humans; Interleukin-8; Lung Neoplasms; NF-kappa B; Nuclear Proteins; Ozone; Protein Kinase C; Protein-Tyrosine Kinases; Reactive Oxygen Species; Signal Transduction; Transcription, Genetic; Tumor Cells, Cultured