Lipopolysaccharide, hypoxia and shear stress, encountered in conditions related to endothelial damage and infection, are associated with increased adrenomedullin levels |
Adrenomedullin immunoreactivity has been reported in bronchial mucosa and glands and type II pneumocytes |
Adrenomedullin is expressed by several immune system cells, including macrophages, monocytes and T-cells, in lymphoid organs, including the lung |
Adrenomedullin downregulates serum and lung levels of a wide spectrum of inflammatory mediators [32], including: |
cytokines (tumour necrosis factor-α, interleukin (IL)-6, IL-1β, IL-12 and interferon-γ) |
chemokines (macrophage inflammatory protein-2 and RANTES) |
serum amyloid A |
nitric oxide |
Adrenomedullin upregulates systemic and local levels of the anti-inflammatory cytokine IL-10 |
Adrenomedullin inhibits neutrophil binding to vascular endothelial cells and subsequent neutrophil emigration in the lung |
Adrenomedullin upregulates β-adrenergic agonist levels, a phenomenon observed in acute asthma and thought to represent a preventive mechanism against bronchoconstriction [31] |
Hypoxia leads to adrenomedullin upregulation through the hypoxia inducible factor-1 pathway, which interacts with nuclear factor κB to promote the expression of inflammatory genes [31, 33–35]. |