A tiered approach to investigate the inhalation toxicity of cobalt substances. Tier 2a: Grouping cobalt compounds based on their capacity to stabilize HIF-1α in human alveolar epithelial cells in vitro.

Excessive inhalation of cobalt (Co) dust can have harmful effects on the respiratory tract, yet all cobalt substances do not have the same potential for inducing toxicity. The prevalent hypothesis is that the potential of Co substances to release Co ions in the organism and in cells drives their toxicity profile. Here, we explored the possibility of grouping Co substances for predicting inhalation toxicity based on in vitro data using the stabilization of hypoxia-inducible factor (HIF)-1α as a read out for intracellular Co ion content.

CCR2 monocytic myeloid-derived suppressor cells (M-MDSCs) inhibit collagen degradation and promote lung fibrosis by producing transforming growth factor-β1.

Monocytes infiltrating scar tissue are predominantly viewed as progenitor cells. Here, we show that tissue CCR2 monocytes have specific immunosuppressive and profibrotic functions. CCR2 monocytic cells are acutely recruited to the lung before the onset of silica-induced fibrosis in mice.