title: Cadmium-induced inflammatory responses in cells relevant for lung toxicity: Expression and release of cytokines in fibroblasts, epithelial cells and macrophages.
abstract: Inhalation is an important route of cadmium (Cd) exposure, and the lung is considered to be one of the main target organs of Cd toxicity. Pulmonary inflammation seems to be involved in development of many lung diseases. In the present study we show that Cd(2+) at fairly low concentrations affects gene expression of several different cytokines/chemokines in human M1 fibroblasts. The chemokines CXCL2, CXCL3, IL-8/CXCL8 and CCL26, the pro-inflammatory cytokine IL-6 and the receptor IL-1RL1 were expressed at high levels after exposure to 7 microM Cd(2+) for 7h. The expression of some important cytokines was further studied in two different primary cell cultures from rat lungs. Cd(2+) induced cytokine responses at low concentrations (3-6 microM) and early time-points both in type 2 epithelial cell-enriched cultures and alveolar macrophages. However, the two primary lung cells displayed different patterns of cytokine release. Cd(2+) induced an increased release of IL-6 and MIP-2/CXCL2 from the epithelial cells and MIP-2, IL-1beta and TNF-alpha from alveolar macrophages. In conclusion, the marked up-regulation of different cytokines in these cell types, that are important in development of lung injury and disease, suggests that inflammation may contribute in Cd-induced lung damage.
authors.affiliation: Norwegian Institute of Public Health, Oslo, Norway. marit.lag@fhi.no
authors.forename: Marit
authors.initials: M
authors.lastname: Låg
authors.forename: Dmitrii
authors.initials: D
authors.lastname: Rodionov
authors.forename: Johan
authors.initials: J
authors.lastname: Ovrevik
authors.forename: Oddmund
authors.initials: O
authors.lastname: Bakke
authors.forename: Per E
authors.initials: PE
authors.lastname: Schwarze
authors.forename: Magne
authors.initials: M
authors.lastname: Refsnes
mesh_terms: D000818:Animals; D002104:Cadmium / Q000633:toxicity*; D002470:Cell Survival / Q000187:drug effects; D016207:Cytokines / Q000235:genetics* / Q000378:metabolism; D004847:Epithelial Cells / Q000187:drug effects / Q000378:metabolism; D005347:Fibroblasts / Q000187:drug effects / Q000378:metabolism; D007249:Inflammation / Q000139:chemically induced*; D053583:Interleukin-1beta / Q000235:genetics; D008168:Lung / Q000187:drug effects*; D008264:Macrophages / Q000187:drug effects / Q000378:metabolism; D008297:Male; D020411:Oligonucleotide Array Sequence Analysis; D016133:Polymerase Chain Reaction; D051381:Rats; D011921:Rats, Inbred WKY; D014409:Tumor Necrosis Factor-alpha / Q000235:genetics
chemical_list: D016207:Cytokines; D053583:Interleukin-1beta; D014409:Tumor Necrosis Factor-alpha; D002104:Cadmium