interleukin-8 and Silicosis

Workers chronically exposed to respirable crystalline silica (CS) are susceptible to adverse health effects like silicosis and lung cancer. This study aimed to investigate potential early peripheral biomarkers of inflammation and oxidative stress in miners. The subjects enrolled in this study were occupationally unexposed workers (OUW, n = 29) and workers exposed to crystalline silica (WECS), composed by miners, which were divided into two subgroups: workers without silicosis (WECS I, n = 39) and workers diagnosed with silicosis, retired from work (WECS II, n = 42). The following biomarkers were evaluated: gene expression of L-selectin, CXCL2, CXCL8 (IL-8), HO-1, and p53; malondialdehyde (MDA) plasma levels and non-protein thiol levels in erythrocytes. Additionally, protein expression of L-selectin was evaluated to confirm our previous findings. The results demonstrated that gene expression of L-selectin was decreased in the WECS I group when compared to the OUW group (p < 0.05). Regarding gene expression of CXCL2, CXCL8 (IL-8), HO-1, and p53, significant fold change decreases were observed in workers exposed to CS in relation to unexposed workers (p < 0.05). The results of L-selectin protein expression in lymphocyte surface corroborated with our previous findings; thus, significant downregulation in the WECS groups was observed compared to OUW group (p < 0.05). The MDA was negatively associated with the gene expression of CXCL-2, CXCL8 (IL-8), and p53 (p < 0.05). The participants with silicosis (WECS II) presented significant increased non-protein thiol levels in relation to other groups (p < 0.05). Taken together, our findings may contribute to help the knowledge about the complex mechanisms involved in the silicosis pathogenesis and in the risk of lung cancer development in workers chronically exposed to respirable CS.

Topics: Adult; Biomarkers; Case-Control Studies; Chemokine CXCL2; Gene Expression; Genes, p53; Heme Oxygenase-1; Humans; Inflammation; Interleukin-8; L-Selectin; Male; Malondialdehyde; Mining; Occupational Exposure; Oxidative Stress; Silicon Dioxide; Silicosis

Instillation of silica into the lungs of rodents results in pathological changes that strongly mimic human silicosis, an occupational lung disease marked by restrictive airway obstruction, inflammation, and fibrosis. Because IL-13 is a pivotal proinflammatory and fibrogenic cytokine, we examined whether a recombinant immunotoxin comprised of human IL-13 and a mutated form of Pseudomonas exotoxin (IL-13-PE) might affect pathological features of experimental silicosis. Mice received a single intranasal instillation of silica particles and were treated with intranasal IL-13-PE every other day from days 21 to 27 postsilica. The sensitivity of putative cell targets to IL-13-PE was also assessed in in vitro settings. Upregulation of IL-13, its receptor subunits IL-13Rα1 and IL-13Rα2, and shared receptor IL-4Rα were associated with development of granulomatous lung inflammation triggered by silica. IL-13-PE inhibited silica-induced granuloma and fibrotic responses noted at 24 h and 15 d after the last treatment. Upregulation of TNF-α, TGF-β, and chemokines, as well as increased collagen deposition and airway hyperreactivity to methacholine were all clearly sensitive to IL-13-PE. In addition, IL-13-PE inhibited both IL-13-induced proliferation of cultured lung fibroblasts from silicotic mice and silica-induced IL-8 generation from A549 cells. In conclusion, our findings show that therapeutic treatment with IL-13-PE can reverse important pathological features caused by inhalation of silica particles, suggesting that this recombinant immunotoxin is a promising molecular template in drug discovery for the treatment of silicosis.

Topics: Administration, Intranasal; Animals; Cell Proliferation; Cells, Cultured; Exotoxins; Fibroblasts; Granuloma; Inflammation; Interleukin-13; Interleukin-4 Receptor alpha Subunit; Interleukin-8; Lung; Lymphotoxin-alpha; Male; Methacholine Chloride; Mice; Pseudomonas; Receptors, Interleukin-13; Recombinant Proteins; Respiratory Hypersensitivity; Silicon Dioxide; Silicosis; Tumor Necrosis Factor-alpha; Up-Regulation

Molecular mechanisms in the pathogenesis of silicosis are not fully understood. Exposure to crystalline silica leads to the activation of signaling pathways controlling the production and secretion of inflammatory mediators. Inflammatory cytokines are noted as important candidate genes for fibrotic lung diseases. Cytokines, chemokines, and variations of their genes have been associated with upregulation or downregulation of chronic inflammatory mediators. Variations in the interleukin (IL)-18, IL-8 and chemokine receptor CXCR2 genes are believed to influence the risk of silicosis in stone-grinding factory workers in Iran. Allele-specific oligonucleotide polymerase chain reaction (PCR) procedure was carried out for IL-18 -137 and IL-18 -607, meanwhile touchdown PCR was performed for IL-8 -251 and CXCR2 +1208 genotyping. Variation in genotypic and allelic frequencies was not statistically different among cases versus controls (p > 0.05). These findings indicated for the first time that IL-18 -137, IL-18 -607, IL-8 -251, and CXCR2 +1208 are suggested not to influence the risk of silicosis in tested occupational group.

Topics: Case-Control Studies; Environmental Exposure; Gene Frequency; Genetic Predisposition to Disease; Genotype; Healthy Volunteers; Humans; Interleukin-18; Interleukin-8; Iran; Male; Polymerase Chain Reaction; Polymorphism, Single Nucleotide; Receptors, Interleukin-8B; Risk Factors; Silicon Dioxide; Silicosis

To explore the relationship between the polymorphisms of interleukin-8 (IL-8) and the silicosis susceptibility.. The case group consisted of 101 male patients with stage I silicosis diagnosed by the Pneumoconiosis Diagnosis Expert Panel according to the Chinese National Diagnosis Criteria of Pneumoconiosis (GBZ 70-2009). The control group consisted of 121 workers without silicosis exposed to same dusts. The cases and the controls had the same dust exposure history. The peripheral venous blood was drawn from each subject. DNA was extracted from leucocytes by the salting method. The polymerase chain reaction restriction fragment length polymorphism (PCR-RFLP) techniques and PCR were used to examine polymorphism of IL-8 (Met31Arg, 781C/T, -251A/T and RA+860).. There were no the differences of age, cumulative exposure time and smoking between the cases and the controls (P > 0.05). The frequencies of IL-8 (Met31Arg) GT genotypes in cases and controls were 12.87% and 2.48%, respectively, there was significant difference (P < 0.05). The frequencies of allele G in cases and controls were 6.44% and 2.07%, respectively, there was significant difference (P < 0.05). The frequencies of IL-8 (-251A/T) AA genotypes in cases and controls were 9.90% and 25.64%, respectively, there was significant difference (P < 0.05). The frequencies of IL-8 (781C/T) CC, CT, TT genotypes in cases and controls were 38.61%, 40.59%, 20.79% and 46.28%, 40.50%, 13.22%, respectively, there was no significant difference (P > 0.05). The frequencies of IL-8 (RA+860) GG, GC and CC genotypes in cases and controls were 75.25%, 21.78%, 2.97%, 80.17%, 14.88%, 4.96%, respectively, there was no significant difference (P > 0.05).. IL-8 (Met31Arg and -251A/T) genetic polymorphisms might play a role in the development of silicosis. The risk of pneumoconiosis in workers carrying (Met31Arg) genotype GT is likely to increase. The risk of pneumoconiosis in workers carrying IL-8 (-251A/T) AA genotype is likely to decrease. The relationship between IL-8 781C/T and RA+860 genes polymorphisms and silicosis is not found.

Topics: Aged; Aged, 80 and over; Case-Control Studies; Dust; Gene Frequency; Genetic Predisposition to Disease; Genotype; Humans; Interleukin-8; Male; Middle Aged; Occupational Exposure; Polymorphism, Single Nucleotide; Silicosis

To study the roles of macrophage apoptosis, IL-1, and IL-8 in the pathogenesis of rat pulmonary fibrosis induced by silica.. Forty eight male Wistar rats were divided into the 4 control groups (24 rats) and 4 experimental groups (24 rats). Rats in the control groups were treated with 1 ml normal saline by trachea instillation, whereas the rats in experimental groups were exposed 1 ml silica suspension (100 mg/ml) by trachea instillation for 1, 7, 14 and 28 days, respectively. Six rats of each group were sacrificed, then the bronchoalveolar lavage fluid and lung tissues were collected, respectively. Pulmonary inflammation, fibrosis and other pathological changes were detected with H.E. staining. Morphological changes of the early stage apoptosis in macrophages were detected with transmission electron microscope (TEM). The early apoptosis rates of macrophages in BALF were also assessed using Annexin V-FITC/PI kit. The IL-1 and IL-8 levels of serum were measured with the ELISA.. The apoptotic rates (11.48% +/- 0.24%, 16.03% +/- 0.68%, 15.53% +/- 1.07%, 18.92% +/- 2.70%, respectively) of macrophage in the experimental groups increased obviously with time, as compared to the controls (5.47% +/- 2.06%, 6.39% +/- 0.215, 9.07% +/- 0.61% and 8.54% +/- 0.16%, Respectively) (P < 0.05). The IL-1 levels of serum in the experimental groups were 23.64 +/- 0.84, 23.38 +/- 1.10, 22.21 +/- 0.86 and 24.29 +/- 1.31 pg/ml, respectively, which were significantly higher than those (18.52 +/- 1.23, 18.40 +/- 1.6, 17.92 +/- 2.21 and 18.53 +/- 2.64 pg/ml, respectively) in the control groups (P < 0.05) without time-effect relationship. The serum IL-8 levels on the 1st, 7th and 14th days in the experimental groups were 21.32 +/- 1.44, 21.90 +/- 2.08 and 22.00 +/- 2.80 pg/ml, respectively, which were significantly higher than those (17.69 +/- 1.09, 16.98 +/- 2.09 and 17.54 +/- 1.62 pg/ml, respectively) in the control groups (P < 0.05).. The early macrophage apoptosis and changes of IL-1 and IL-8 may in lungs may play an important role in the development of pulmonary fibrosis induced by silica.

Topics: Animals; Apoptosis; Disease Models, Animal; Interleukin-1; Interleukin-8; Macrophages, Alveolar; Male; Pulmonary Fibrosis; Rats; Rats, Wistar; Silicon Dioxide; Silicosis

Little is known about the crucial mediators involved in the inflammation and fibrogenesis in bagassosis. The aim of this study was to characterize the cellular and cytokine patterns in the airways of bagassosis and to compare these with silicosis subjects and controls.. Bronchoalveolar lavage (BAL) was performed in 11 patients with bagassosis, 16 cases with silicosis, and 8 controls. Differential cell counts, total protein concentration, TNF-alpha, IL-1beta, IL-5, IL-6, and IL-8 were analyzed in the bronchoalveolar lavage fluid (BALF).. Bagassosis was characterized with hypercellularity with neutrophilia in BALF; while the predominant cell in the BALF in silicosis was macrophage. Compared with control subjects, increased TNF-alpha, IL-1beta, IL-8, and IL-6 levels were found in the BALFs in both bagassosis and silicosis. Furthermore, IL-6 levels in the BALF of silicosis subjects were significantly higher than that seen in bagassosis. In contrast, bagassosis had higher level of IL-8 in BALF than that in silicosis. Relationship among these parameters were found between IL-8 levels and neutrophils, lymphocytes and IL-1 beta in bagassosis, macrophages and IL-1beta in silicosis. No significant differences of total protein concentrations and IL-5 in BALF were found between controls or bagassosis, and silicosis.. The findings of this study suggest that neutrophils, TNF-alpha, IL-1beta, IL-8, and IL-6 are involved in the pathogenesis in bagassosis. The mechanisms underline the different cellular and cytokine profiles in bagassosis and silicosis warrant further investigation.

Topics: Adult; Bronchoalveolar Lavage Fluid; Cytokines; Enzyme-Linked Immunosorbent Assay; Humans; Interleukin-1; Interleukin-6; Interleukin-8; Male; Middle Aged; Pneumoconiosis; Silicosis; Tumor Necrosis Factor-alpha