Profiling Distinctive Inflammatory and Redox Responses to Hydrogen Sulfide in Stretched and Stimulated Lung Cells

Hydrogen sulfide (H(2)S) protects against stretch-induced lung injury. However, the impact of H(2)S on individual cells or their crosstalk upon stretch remains unclear. Therefore, we addressed this issue in vitro using relevant lung cells. We have explored (i) the anti-inflammatory properties of H(2)S on epithelial (A549 and BEAS-2B), macrophage (RAW264.7) and endothelial (HUVEC) cells subjected to cycling mechanical stretch; (ii) the intercellular transduction of inflammation by co-culturing epithelial cells and macrophages (A549 and RAW264.7); (iii) the effect of H(2)S on neutrophils (Hoxb8) in transmigration (co-culture setup with HUVECs) and chemotaxis experiments. In stretched epithelial cells (A549, BEAS-2B), the release of interleukin-8 was not prevented by H(2)S treatment. However, H(2)S reduced macrophage inflammatory protein-2 (MIP-2) release from unstretched macrophages (RAW264.7) co-cultured with stretched epithelial cells. In stretched macrophages, H(2)S prevented MIP-2 release by limiting nicotinamide adenine dinucleotide phosphate oxidase-derived superoxide radicals (ROS). In endothelial cells (HUVEC), H(2)S inhibited interleukin-8 release and preserved endothelial integrity. In neutrophils (Hoxb8), H(2)S limited MIP-2-induced transmigration through endothelial monolayers, ROS formation and their chemotactic movement. H(2)S induces anti-inflammatory effects in a cell-type specific manner. H(2)S limits stretch- and/or paracrine-induced inflammatory response in endothelial, macrophage, and neutrophil cells by maintaining redox homeostasis as underlying mechanism.