Subtoxic Doses of Cadmium Modulate Inflammatory Properties of Murine RAW 264.7 Macrophages.
Cadmium (Cd) is a toxic heavy metal that exhibits various adverse effects in the human and animal organism. Its resemblance to essential metals such as calcium, iron, and zinc leads to an unintended uptake in cells after intake through inhalation and ingestion. In this study we investigated the toxicity and the immunomodulatory potential of Cd in nonactivated and activated murine macrophages (i.e., cell line RAW 264.7). Cadmium alone caused a dose-dependent decreased viability of exposed cells. Subtoxic Cd concentrations delayed cell death in macrophages, resulting from cytotoxic storm, producing reactive oxygen species (ROS) and nitric oxide (NO), in response to their stimulation by bacterial antigens via pattern-recognition receptors (PRRs). In addition, production of selected pro- and anti-inflammatory cytokines, the chemokine CXCL1 (KC), and NO was determined. We observed that proinflammatory IL-1β and also CXCL1 were highly upregulated whereas anti-inflammatory or regulatory cytokines IL-6 and IL-10 were suppressed by 10 µM Cd. Also production of antibacterial NO was significantly reduced through exposure to 10 µM Cd, maybe explaining better survival of macrophages. Additionally, we could show by analysis via ICP-MS that different effects of Cd in nonactivated and activated macrophages definitely did not result from different Cd uptake rates.
Fraunhofer Institute for Cell Therapy and Immunology (IZI), 04103 Leipzig, Germany.
Sina
S
Riemschneider
Martin Luther University of Halle-Wittenberg, Institute for Biology/Microbiology, 06120 Halle, Germany.
Martin
M
Herzberg
Fraunhofer Institute for Cell Therapy and Immunology (IZI), 04103 Leipzig, Germany.
Jörg
J
Lehmann
D000818:Animals; D000942:Antigens, Bacterial / Q000494:pharmacology; D002104:Cadmium / Q000633:toxicity*; D002460:Cell Line; D002470:Cell Survival / Q000187:drug effects* / Q000235:genetics; D054360:Chemokine CXCL1 / Q000096:biosynthesis; D005786:Gene Expression Regulation / Q000187:drug effects; D006801:Humans; D056747:Immunomodulation / Q000187:drug effects; D007249:Inflammation / Q000139:chemically induced / Q000235:genetics* / Q000473:pathology; D016753:Interleukin-10 / Q000096:biosynthesis; D053583:Interleukin-1beta / Q000096:biosynthesis; D015850:Interleukin-6 / Q000096:biosynthesis / Q000378:metabolism; D008264:Macrophages / Q000187:drug effects* / Q000378:metabolism; D051379:Mice; D009569:Nitric Oxide / Q000378:metabolism*; D017382:Reactive Oxygen Species / Q000378:metabolism
D000942:Antigens, Bacterial; D054360:Chemokine CXCL1; C475895:Cxcl1 protein, mouse; C508609:IL10 protein, human; C587672:IL1B protein, mouse; D053583:Interleukin-1beta; D015850:Interleukin-6; D017382:Reactive Oxygen Species; D002104:Cadmium; D016753:Interleukin-10; D009569:Nitric Oxide