RESUMO
BACKGROUND: Gasoline is a complex mixture of saturated and unsaturated hydrocarbons, in which aromatic compounds, such as BTX (benzene, toluene, and xylene) feature as the main constituents. Simultaneous exposure to these aromatic hydrocarbons causes a significant impact on benzene toxicity. In order to detect early alterations caused in gasoline station attendants exposed to BTX compounds, immunological, inflammatory, and oxidative stress biomarkers were evaluated. METHODS: A total of 66 male subjects participated in this study. The gasoline station attendants (GSA) group consisted of 38 gasoline station attendants from Rio Grande do Sul, Brazil. The non-exposed group consisted of 28 subjects who were non-smokers and who had no history of occupational exposure. Environmental and biological monitoring of BTX exposure was performed using blood and urine. RESULTS: The GSA group showed increased BTX concentrations in relation to the non-exposed group (p < 0.001). The GSA group showed elevated protein carbonyl (PCO) levels and pro-inflammatory cytokines, decreased expression of CD80 and CD86 in monocytes, and reduced glutathione S-transferase (GST) activity compared to the non-exposed group (p < 0.05). BTX levels and trans,trans-muconic acid levels were positively correlated with pro-inflammatory cytokines and negatively correlated with interleukin-10 contents (p < 0.001). Increased levels of pro-inflammatory cytokines were accompanied by increased PCO contents and decreased GST activity (p < 0.001). Furthermore, according to the multiple linear regression analysis, benzene exposure was the only factor that significantly contributed to the increased pro-inflammatory cytokines (p < 0.05). CONCLUSIONS: Taken together, these findings show the influence of exposure to BTX compounds, especially benzene, on the immunological, inflammatory, and oxidative stress biomarkers evaluated. Furthermore, the data suggest the relationship among the evaluated biomarkers of effect, which could contribute to providing early signs of damage to biomolecules in subjects occupationally exposed to BTX compounds.
Assuntos
Poluentes Ocupacionais do Ar/análise , Derivados de Benzeno/urina , Monitoramento Biológico/métodos , Citocinas/urina , Biomarcadores Ambientais/imunologia , Exposição Ocupacional/análise , Estresse Oxidativo/efeitos dos fármacos , Adulto , Poluentes Ocupacionais do Ar/efeitos adversos , Antígeno B7-1/sangue , Antígeno B7-1/urina , Antígeno B7-2/sangue , Antígeno B7-2/urina , Derivados de Benzeno/toxicidade , Brasil , Citocinas/sangue , Biomarcadores Ambientais/efeitos dos fármacos , Humanos , Masculino , Exposição Ocupacional/efeitos adversos , Estresse Oxidativo/imunologia , Carbonilação Proteica/efeitos dos fármacosRESUMO
Ouabain is a steroid capable of binding to and inhibiting Na(+),-K(+)-ATPase. Studies have demonstrated some actions of ouabain on immune cells, which indicated both pro- and anti-inflammatory properties of this molecule. Nevertheless, its effects on human monocytes are still poorly understood. Thus, the present work investigated effects of ouabain in the activation and function of human adherent monocytes. Our results show that there is an increase in intracellular calcium levels already 5 minutes following monocyte treatment with 10(-7) M of ouabain. Furthermore, monocytes expressed increased amounts of surface activation markers such as CD69, HLA-DR, CD86, and CD80 and also presented an augmented endocytic activity of dextran-FITC particles after 24 hours of culture in the presence of ouabain. However, monocytes treated with ouabain did not have an increased stimulatory capacity in allogeneic mixed leukocyte reaction. Ouabain-treated monocytes produced higher levels of IL-1 ß and TNF- α as reported before. A novel observation was the fact that ouabain induced IL-10 and VEGF as well. Collectively, these results suggest that ouabain impacts monocyte activation and modulates monocyte functions, implying that this steroid could act as an immunomodulator of these cells.
Assuntos
Citocinas/metabolismo , Endocitose , Inibidores Enzimáticos/farmacologia , Monócitos/efeitos dos fármacos , Monócitos/patologia , Ouabaína/farmacologia , Antígenos CD/sangue , Antígenos de Diferenciação de Linfócitos T/sangue , Antígeno B7-1/sangue , Antígeno B7-2/sangue , Citometria de Fluxo , Regulação da Expressão Gênica , Antígenos HLA-DR/sangue , Voluntários Saudáveis , Humanos , Interleucina-1beta/sangue , Lectinas Tipo C/sangue , Leucócitos Mononucleares/citologia , Teste de Cultura Mista de Linfócitos , Monócitos/citologia , Fator de Necrose Tumoral alfa/sangueRESUMO
Leishmaniasis is an important tropical disease composed of several clinical forms that adversely affect millions of people globally. Critical cells involved in the host-Leishmania interaction are monocytes and macrophages, which act to protect against infections due to their ability to both control intracellular infections and regulate the subsequent adaptive immune response. Both soluble factors and cell surface receptors are keys in directing the immune response following interaction with pathogens such as Leishmania. Toll-like receptors (TLRs) have an essential role in immune responses against infections, but little is known about their role in human infection with Leishmania braziliensis. In this work, we evaluated peripheral blood CD14+ monocytes for the expression of immunoregulatory cytokines, co-stimulatory molecules and TLR9 from cutaneous leishmaniasis patients infected with L. braziliensis and noninfected individuals. Our results showed that patients present decreased expression of co-stimulatory molecules such as CD80 and CD86 following culture with media alone or after stimulus with soluble Leishmania antigen. Interestingly, TLR9 expression was higher after culture with soluble Leishmania antigen (SLA), suggesting a role of this molecule in immunoregulation of active disease. Lastly, higher frequencies of TLR9+ monocytes were correlated with greater lesion size. These findings demonstrate a peripheral monocytes profile compatible with important immunoregulatory potential.