Calcium dependent and independent cytokine synthesis by air pollution particle-exposed human bronchial epithelial cells

• Published in: Toxicology and applied pharmacology 2007-12, Vol.225 (2), p.134-141
• Main Authors: Sakamoto, Noriho, Hayashi, Shizu, Gosselink, John, Ishii, Hiroshi, Ishimatsu, Yuji, Mukae, Hiroshi, Hogg, James C., van Eeden, Stephan F.
• Format: Article
• Language: English
• Subjects: 60 APPLIED LIFE SCIENCES; Aged; Aged, 80 and over; Air; Air Pollutants - chemistry; Air Pollutants - toxicity; AIR POLLUTION; Biological and medical sciences; Bronchi - cytology; Bronchi - immunology; Bronchial epithelial cells; CALCIUM; Calcium - metabolism; CALCIUM IONS; Cells, Cultured; CESIUM FLUORIDES; Cytokine; Cytokines - biosynthesis; Cytokines - drug effects; Cytosol - metabolism; DISEASE INCIDENCE; Dose-Response Relationship, Drug; Environmental pollutants toxicology; ENZYME IMMUNOASSAY; Enzyme-Linked Immunosorbent Assay; Epithelial Cells - drug effects; Epithelial Cells - immunology; EPITHELIUM; Fluorescent Dyes; Fura-2; Granulocyte-Macrophage Colony-Stimulating Factor - biosynthesis; Granulocyte-Macrophage Colony-Stimulating Factor - drug effects; Humans; INFLAMMATION; Inflammation Mediators - metabolism; Interleukin-1beta - biosynthesis; Interleukin-1beta - drug effects; Interleukin-8 - biosynthesis; Interleukin-8 - drug effects; LANTHANUM CHLORIDES; Leukemia Inhibitory Factor - biosynthesis; Leukemia Inhibitory Factor - drug effects; LITHIUM FLUORIDES; Medical sciences; Middle Aged; MORTALITY; NICKEL CHLORIDES; Particle Size; Particulate matter air pollution; POLYMERASE CHAIN REACTION; PROTEINS; Toxicology
• ISSN: 0041-008X; 1096-0333
• DOI: 10.1016/j.taap.2007.07.006

Exposure to ambient air pollution particles with a diameter of < 10 μm (PM 10) has been associated with increased cardiopulmonary morbidity and mortality. We have shown that human bronchial epithelial cells (HBECs) exposed to PM 10 produce pro-inflammatory mediators that contribute to a local and systemic inflammatory response. Changes in intracellular calcium concentrations ([Ca 2+] i) have been demonstrated to regulate several functions of the airway epithelium including the production of pro-inflammatory mediators. The aim of the present study was to determine the nature and mechanism of calcium responses induced by PM 10 in HBECs and its relationship to cytokine synthesis. Primary HBECs were exposed to urban air pollution particles (EHC-93) and [Ca 2+] i responses were measured using the fluoroprobe (Fura-2). Cytokine levels were measured at mRNA and protein levels using real-time PCR and ELISA. PM 10 increased [Ca 2+] i in a dose-dependent manner. This calcium response was reduced by blocking the influx of calcium into cells (i.e. calcium-free medium, NiCl 2, LaCl 3). PM 10 also decreased the activity of calcium pumps. PM 10 increased the production of IL-1β, IL-8, GM-CSF and LIF. Preincubation with intracellular calcium chelator (BAPTA-AM) attenuated IL-1β and IL-8 production, but not GM-CSF and LIF production. We conclude that exposure to PM 10 induces an increase in cytosolic calcium and cytokine production in bronchial epithelial cells. Our results also suggest that PM 10 induces the production of pro-inflammatory mediators via either intracellular calcium-dependent (IL-1β, IL-8) or -independent (GM-CSF, LIF) pathways.